Osteoporosis

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ONGOING

not glucocorticoid-induced: women

postmenopausal with fragility fracture or DXA T-score ≤-2.5 or osteopenia and at high to very high risk of fracture

1st line – bisphosphonate

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1st line –

bisphosphonate

Bisphosphonates (e.g., alendronic acid, ibandronic acid, risedronate, zoledronic acid) are the first-line treatment for postmenopausal women at high risk of fracture with prior hip or vertebral fractures and/or dual-energy x-ray absorptiometry (DXA) T-score of ≤-2.5, or T-score between -1.0 and -2.5 and increased risk of fracture, as determined by a formal clinical risk assessment tool.[62][67][70][108] Bisphosphonates may also be used for women with a very high risk of fracture (e.g., very low T-score and a history of severe or multiple vertebral fractures, a recent fracture, or multiple risk factors for fracture), but guidelines recommend initial treatment with an anabolic agent as the preferred option for these patients.[67][70][81][113][114]

Oral bisphosphonates reduce the risk of fracture in women with prior fragility fractures.[115][116] They effectively increase bone mineral density (BMD) and decrease risk of vertebral and non-vertebral fractures.[110][111] This is with the exception of ibandronic acid, which has only been shown to decrease the risk of femoral fracture in high-risk populations with a femoral neck BMD T-score of -3 or less by post-hoc analysis.[112]

Ibandronic acid may reduce vertebral fracture but its effects in reducing hip fracture and non-vertebral fracture are uncertain, and it is therefore not recommended for these indications in postmenopausal women.[108] Intravenous ibandronic acid has been shown to be effective in increasing BMD in the treatment and prevention of postmenopausal osteoporosis.[130][131]

One study demonstrated that 6 years of treatment with zoledronic acid maintained BMD, decreased vertebral fracture, and reduced bone turnover marker compared with 3 years of treatment.[132] In an extension study, those who were treated with zoledronic acid for 6 years were randomised to either continue zoledronic acid for a further 3 years or switched to placebo. The extension study found no significant decrease in the number of fractures between the two groups.[133] In an observational follow-up of older women with osteopenia randomised to receive zoledronic acid or placebo at 18-month intervals for 6 years, reduced fracture rates were maintained for 1.5 to 3.5 years after the last zoledronic acid infusion, but were similar to the placebo group thereafter.[139] Zoledronic acid exerts a faster effect in the prevention of vertebral fractures and a slower onset effect in the prevention of hip fractures.[134][135][136]

Conflicting results have been reported concerning the risk of serious atrial fibrillation in women treated with zoledronic acid. Systematic reviews of randomised controlled trials and observational studies showed significantly increased risk of new-onset atrial fibrillation with both intravenous and oral bisphosphonates.[137][140] However, studies did not show evidence of increased comorbidities such as stroke or death. Overall, the risk-benefit balance outweighs such complications in this population.[138]

A drug holiday for patients with a low to moderate risk of fracture should be considered for patients who are stable after 5 years of treatment with oral bisphosphonates, or after 3 years of treatment with zoledronic acid.[70]

For patients at high risk of fracture, longer treatment of up to 10 years with oral bisphosphonates or up to 6 years with zoledronic acid is suggested.[70]

Adverse effects of oral bisphosphonates primarily relate to the upper gastrointestinal tract and include difficulty swallowing, oesophagitis, and gastric ulcers. Joint and muscular pain, osteonecrosis of the jaw, and atypical femoral fractures have also been reported.[117][118][119][120][121][122] One large systematic review and meta-analysis of more than 650,000 patients demonstrated an increased risk of atypical fractures with bisphosphonates.[119] Further research concluded that the benefits of bisphosphonate treatment outweigh the risk of atypical femur fracture, particularly in patients treated for 3-5 years.[123] Consensus is emerging about strategies to prevent atypical femur fracture in patients treated with bisphosphonates, including drug holidays after 5 years' use in some patients.[123]

Oral bisphosphonates must be taken in the morning on an empty stomach with at least 240 mL (8 oz) of water and at least 30 minutes before eating, as food decreases absorption. Patient should remain upright when taking the drug.

Primary options

alendronic acid: 10 mg orally once daily; or 70 mg orally once weekly

risedronate sodium: 5 mg orally once daily; or 35 mg orally once weekly; or 75 mg orally on 2 consecutive days once monthly; or 150 mg orally once monthly

ibandronic acid: 150 mg orally once monthly; or 3 mg intravenously once every 3 months

zoledronic acid: 5 mg intravenously once annually

Plus – calcium and vitamin D supplementation

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Plus –

calcium and vitamin D supplementation

Treatment recommended for ALL patients in selected patient group

Patients with osteoporosis should be advised to consume the recommended daily allowance of calcium and vitamin D through diet, supplementation, or both.[62][70] Adequate calcium intake is necessary to maintain bone health, and vitamin D facilitates dietary calcium absorption.[62]

Evidence of the effect of calcium and vitamin D supplementation on fracture risk is mixed. One systematic review demonstrated that calcium and vitamin D supplementation significantly reduced the incidence of fractures and enhanced bone mineral density (BMD) in older adults compared with the control group.[92] Another systematic review of randomised controlled trials and observational studies of calcium intake with fractures as an end point showed that dietary calcium intake is not associated with risk of fractures, and there is no clinical trial evidence that increasing calcium intake from dietary sources prevents fractures. Moreover, evidence that calcium supplements prevent fractures was weak and inconsistent.[93] In subsequent letters to the editors, it is argued that the results of these trials cannot be applied to a specifically targeted frail, older population that may benefit from calcium supplementation.

Patient tolerance determines calcium formulation given.

Adverse effects of calcium supplements are primarily gastrointestinal and include increased moderate to severe constipation, bloating, and wind.[35] Nephrolithiasis may also occur.[35]

Primary options

ergocalciferol: 700-800 units orally once daily

and

calcium: adults 51-70 years of age: 1200 mg/day orally

Consider – exercise

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Consider –

exercise

Additional treatment recommended for SOME patients in selected patient group

For those who are able, regular weight-bearing exercise is recommended to maintain bone strength, and exercises that enhance balance may help to prevent falls.[62][81][98] Guidelines recommend progressive muscle resistance training plus balance and functional training at least 2 days per week for fall and fracture prevention.[98][99] Patients with vertebral fractures, multiple low-trauma fractures, or frailty may have a higher risk of injury and require tailored advice and supervision.[98]

Evidence from systematic reviews has demonstrated that patients with osteoporosis may safely participate in exercise programmes, and that exercise may improve bone mineral density (BMD) and reduce the risk of falls.[100][101][102][103] However, the exact type of activity and its intensity, duration, and frequency are still unclear.[101][104][105][106] Supervised exercise programmes may reduce the risk of fractures more effectively.[107]

1st line – denosumab

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1st line –

denosumab

Denosumab is approved for the treatment of postmenopausal women with osteoporosis who are at high risk for fracture, and osteoporosis prophylaxis in women at high risk for fracture after receiving adjuvant aromatase inhibitor therapy for breast cancer. Denosumab may also be used for women with a very high risk of fracture (e.g., very low T-score and a history of severe or multiple vertebral fractures, a recent fracture, or multiple risk factors for fracture), but guidelines recommend initial treatment with an anabolic agent as the preferred option for these patients.[67][70][81][113][114]

Denosumab should be used with caution in patients with pre-existing hypocalcaemia or who are at high risk of hypocalcaemia (vitamin D deficient), and in patients with severe renal disease, including end-stage renal disease.[62][108] The US Food and Drug Administration (FDA) has warned of an increased risk of severe hypocalcaemia in patients with advanced chronic kidney disease who are receiving denosumab.[141] Two safety studies showed a significant increase in the risk of severe hypocalcaemia in patients treated with denosumab compared with those treated with bisphosphonates, with the highest risk reported in patients with advanced kidney disease, particularly those on dialysis.[141][142] Severe hypocalcaemia was more common in those with mineral and bone disorder. Patients with advanced chronic kidney disease taking denosumab are at risk of serious outcomes from severe hypocalcaemia, including hospitalisation and death. Before prescribing denosumab, healthcare professionals should assess kidney function and calcium levels, and consider other treatment options for patients at risk. During treatment, frequent monitoring and prompt management of hypocalcaemia are essential.

The Endocrine Society recommends denosumab as an alternative initial treatment in postmenopausal women with osteoporosis who are at high risk for osteoporotic fractures.[108] The effects of denosumab on bone remodelling, reflected in bone turnover markers, reverse after 6 months if the drug is not taken on schedule; therefore, a drug holiday or treatment interruption is not recommended with this agent.[108]

The American College of Obstetrics and Gynecology recommends denosumab as an initial therapy for postmenopausal patients at an increased risk of fracture who prefer 6-monthly subcutaneous administration.[70]

The American College of Physicians recommends denosumab as a second-line treatment to reduce the risk of fracture in postmenopausal women with primary osteoporosis who have contraindications to or experience adverse effects with bisphosphonates.[67]

Fracture risk should be reassessed after 5-10 years of treatment and those women with a high risk of fracture should continue treatment with denosumab or be treated with other osteoporotic treatment.[108]

The FREEDOM trial demonstrated that denosumab given for 36 months was associated with reduction in the risk of vertebral, non-vertebral, and hip fractures in women with osteoporosis who had a bone mineral density (BMD) T-score of -2.5 but not less than -4.0 at the lumbar spine or total hip, compared with placebo.[143]

Extension studies of the FREEDOM trial reported that denosumab treatment of postmenopausal osteoporosis for up to 8 years was associated with persistent reduction of bone turnover, continued increase in BMD, low fracture incidence, and high benefit-risk profile; denosumab treatment for up to 10 years was associated with low rates of adverse events, low incidence of fracture compared with that observed during the original trial, and continued increases in BMD without plateau; discontinuation of denosumab is followed by rapidly rising turnover markers, decreasing bone density, and increasing vertebral fracture risk, suggesting that patients who discontinue denosumab should transition quickly to an alternative antiresorptive treatment.[144][145][146]

There is some evidence to suggest that zoledronic acid given after denosumab is most effective 7-8 months post denosumab discontinuation, and that teriparatide given either prior to or in combination with denosumab increases BMD.[147][148][149] However, further research is needed.[62]

Denosumab has been reported to be significantly more effective at increasing BMD in postmenopausal women previously treated with bisphosphonates, and has demonstrated significant improvement of BMD in at the lumbar spine, total hip, and femoral neck at 12 and 24 months in patients with low BMD or osteoporosis compared with bisphosphonates.[150][151] In patients aged 50 years and older with osteoporosis, denosumab was found to be as effective as zoledronic acid at reducing the risk of fractures.[152]

An increased risk of serious infection has been reported in patients treated with denosumab compared with placebo.[153][154] However, the overall risk of infection is comparable with other osteoporosis treatments, including bisphosphonates.[153][154] Denosumab has been associated with osteonecrosis of the jaw, impairment of fracture healing, and atypical femoral fractures.[62][67]

Denosumab is not associated with increased risk of cardiovascular outcomes compared with placebo or active comparators.[152][155]

Primary options

denosumab: 60 mg subcutaneously every 6 months

Plus – sequential therapy

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Plus –

sequential therapy

Treatment recommended for ALL patients in selected patient group

In postmenopausal women with osteoporosis taking denosumab, administration should not be delayed or stopped without subsequent antiresorptive therapy (e.g., bisphosphonate, hormone therapy, or selective oestrogen receptor modulator [SERM]) or other therapy administered to prevent a rebound in bone turnover and to decrease the risk of rapid bone mineral density (BMD) loss and an increased risk of fracture.[62][70]

Plus – calcium and vitamin D supplementation

Back

Plus –

calcium and vitamin D supplementation

Treatment recommended for ALL patients in selected patient group

Patient tolerance determines calcium formulation given.

Adverse effects of calcium supplements are primarily gastrointestinal and include increased moderate to severe constipation, bloating, and wind.[35] Nephrolithiasis may also occur.[35]

Primary options

ergocalciferol: 700-800 units orally once daily

and

calcium: adults 51-70 years of age: 1200 mg/day orally

Consider – exercise

Back

Consider –

exercise

Additional treatment recommended for SOME patients in selected patient group

1st line – anabolic agent

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1st line –

anabolic agent

Anabolic agents include teriparatide, abaloparatide, and romosozumab. Teriparatide and abaloparatide are parathyroid hormone analogues approved to treat osteoporosis in postmenopausal women. Romosozumab, a monoclonal antibody sclerostin inhibitor that decreases bone resorption and increases bone formation, is approved for the treatment of osteoporosis in postmenopausal women at high risk for fracture (defined as a history of osteoporotic fracture, or multiple risk factors for fracture), or patients who have failed or are intolerant to other available osteoporosis therapy.

Guidelines recommend initial treatment with an anabolic agent for postmenopausal women with a very high risk of fracture, such as those with a very low T-score and a history of severe or multiple vertebral fractures, a recent fracture, or multiple risk factors for fracture.[62][67][70][81][108][113] They may also be used for those who continue to sustain fractures or have significant bone loss while taking antiresorptive therapy.[70] Anabolic agents are not typically used as initial therapy in patients with a high risk of fractures.

One meta-analysis found that teriparatide and romosozumab were more effective than oral bisphosphonates for reducing the risk of clinical and vertebral fractures regardless of baseline fracture risk indicators (history of previous fractures, age, spine T-score, body mass index [BMI], fracture risk assessment tool [FRAX] score for major osteoporotic fractures).[156] However, guidelines suggest initial treatment with an anabolic agent may be most beneficial for patients with a very high risk of fractures in practice, in part because anabolic agents require subcutaneous administration.[81][99][157]

The American College of Physicians (ACP) guideline only recommends teriparatide or romosozumab for women with primary osteoporosis and a very high risk of fracture; they concluded that evidence for or against abaloparatide treatment was inconclusive.[67] The ACP suggests that postmenopausal women with prevalent vertebral fractures benefit more from teriparatide treatment than those without prevalent fractures.[67]

The Royal Australian College of General Practitioners guideline recommends romosozumab as the preferred first-line option for patients with a very high risk of fracture, based on evidence that it may increase BMD more effectively than alendronic acid or teriparatide.[81]

Romosozumab is recommended for the treatment of postmenopausal osteoporosis for up to 1 year. Romosozumab should be avoided in patients with a high risk for cardiovascular disease or stroke.[81][108][113] Some evidence suggests that romosozumab may have a lower rate of adverse effects compared with alendronic acid and a similar safety profile to bisphosphonates; however, most studies agree that further research is needed to establish the risk of cardiovascular disease with romosozumab treatment.[161][162][163][164][165]

Guidelines recommend treatment with teriparatide or abaloparatide for up to 2 years.[62][70][108] Teriparatide treatment for more than 2 years can be considered if the patient remains or returns to having a high risk of fracture.[62]

The Bone Health and Osteoporosis Foundation (BHOF) suggests that teriparatide and abaloparatide should be avoided in patients at an increased risk of osteosarcoma (Paget’s disease of the bone, prior radiotherapy involving the skeleton, history of bone metastases or malignancies, unexplained elevated alkaline phosphatase, and hereditary disorders predisposing to osteosarcoma).[62]

Adverse effects of teriparatide include leg cramps, nausea, and dizziness, and for abaloparatide they include nausea, postural hypotension, dizziness, headache, and palpitations.[62][108]

Primary options

romosozumab: 210 mg subcutaneously once monthly for 12 months

teriparatide: 20 micrograms subcutaneously once daily

abaloparatide: 80 micrograms subcutaneously once daily

Plus – sequential therapy

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Plus –

sequential therapy

Treatment recommended for ALL patients in selected patient group

When treatment with an anabolic agent is stopped, bone loss can be rapid and alternative agents should be considered to maintain bone mineral density (BMD).[62][113] The Bone Health and Osteoporosis Foundation and the Endocrine Society recommend that teriparatide or abaloparatide treatment is followed with an antiresorptive agent, usually a bisphosphonate, to maintain or further increase BMD.[62][108] Treatment with romosozumab should also be followed by sequential therapy with an antiresorptive agent to maintain BMD gains and reduce the risk of fracture.[67][108][113]

Plus – calcium and vitamin D supplementation

Back

Plus –

calcium and vitamin D supplementation

Treatment recommended for ALL patients in selected patient group

Patient tolerance determines calcium formulation given.

Adverse effects of calcium supplements are primarily gastrointestinal and include increased moderate to severe constipation, bloating, and wind.[35] Nephrolithiasis may also occur.[35]

Primary options

ergocalciferol: 700-800 units orally once daily

and

calcium: adults 51-70 years of age: 1200 mg/day orally

Consider – exercise

Back

Consider –

exercise

Additional treatment recommended for SOME patients in selected patient group

bisphosphonate, denosumab, or anabolic agent not tolerated or contraindicated

1st line – selective oestrogen receptor modulator (SERM)

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1st line –

selective oestrogen receptor modulator (SERM)

Raloxifene and bazedoxifene are licensed in Europe for the treatment of osteoporosis, but bazedoxifene is only available as a combination formulation with conjugated oestrogens in the US.

Raloxifene is approved for the treatment and prevention of osteoporosis in postmenopausal women. It reduces the risk of vertebral fractures in postmenopausal women with osteoporosis.[177] There is no evidence for reduction of non-vertebral fractures. However, its use is associated with an increased risk of venous thrombosis and stroke.[62] Possibility of adverse effects is weighed against potential benefits of reduced risk of vertebral fracture and oestrogen receptor-positive breast cancer.

The American College of Obstetrics and Gynecology suggests raloxifene for postmenopausal patients at increased risk of vertebral fracture and breast cancer who are at low risk of venous thromboembolism and do not have significant vasomotor symptoms.[70]

The American College of Physicians concluded that there is insufficient evidence to recommend for or against treatment with raloxifene or bazedoxifene.[67]

The Endocrine Society recommends raloxifene or bazedoxifene (not available as a single-ingredient formulation in the US) to reduce the risk of vertebral fracture in postmenopausal women who have no vasomotor symptoms with osteoporosis at high risk of fracture and who have a low risk of deep vein thrombosis, for whom bisphosphonates or denosumab are not appropriate, or have a high risk of breast cancer.[108]

The Endocrine Society also recommends a SERM first line for women over the age of 60 years.[108]

One systematic review demonstrated that raloxifene is effective at improving lumbar spine bone mineral density (BMD) in postmenopausal women with end-stage renal disease compared with placebo, with a mean duration of treatment of 12 months.[178] No adverse effects were reported in the raloxifene patient group, but further large randomised controlled trials are needed to evaluate the long-term safety of raloxifene in these patients.[178]

Primary options

raloxifene: 60 mg orally once daily

bazedoxifene: 20 mg orally once daily

Plus – calcium and vitamin D supplementation

Back

Plus –

calcium and vitamin D supplementation

Treatment recommended for ALL patients in selected patient group

Patient tolerance determines calcium formulation given.

Adverse effects of calcium supplements are primarily gastrointestinal and include increased moderate to severe constipation, bloating, and wind.[35] Nephrolithiasis may also occur.[35]

Primary options

ergocalciferol: 700-800 units orally once daily

and

calcium: adults 51-70 years of age: 1200 mg/day orally

Consider – exercise

Back

Consider –

exercise

Additional treatment recommended for SOME patients in selected patient group

2nd line – hormone replacement therapy (HRT)

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2nd line –

hormone replacement therapy (HRT)

Oestrogen decline at menopause is strongly associated with the decrease in bone mineral density (BMD).[2][3] There are various forms of HRT. Oestrogen, either alone or in combination with a progestin, is considered only for women at high risk of osteoporotic fractures for whom non-hormonal therapy is inappropriate.

The Endocrine Society recommends oestrogen as a first-line treatment to prevent all types of fracture for women under 60 years of age (<10 years past menopause) with hysterectomy at high risk of osteoporotic fracture, with a low risk of deep vein thrombosis, for whom bisphosphonates or denosumab are not appropriate, who have vasomotor symptoms, who have no contraindications, no prior myocardial infarction, stroke, or breast cancer, and are willing to take menopausal hormone therapy.[108]

Women who have a uterus should use oestrogen only in combination with a progestin because using oestrogen alone increases the incidence of endometrial cancer.[184]

HRT reduces the incidence of fracture. However, there are increases in risk of coronary heart disease, breast cancer, venous thrombosis, and stroke.[183]

The Endocrine Society recommends oestrogen plus a progestin or tibolone (not available in the US) as a first-line treatment to prevent vertebral and non-vertebral fractures for women with a uterus aged under 60 years (or <10 years past menopause) at high risk of osteoporotic fracture, with a low risk of deep vein thrombosis, for whom bisphosphonates or denosumab are not appropriate, who have vasomotor symptoms, who have no contraindications, no prior myocardial infarction, stroke, or breast cancer, and are willing to take menopausal tibolone therapy.[108]

The Endocrine Society recommends oestrogen plus a progestin or tibolone as a second-line treatment to prevent vertebral and non-vertebral fractures for women aged over 60 years in whom a bisphosphonate, denosumab, and teriparatide/abaloparatide are not appropriate.[108]

The American College of Physicians recommends against using menopausal oestrogen alone or in combination with progestin therapy for the treatment of osteoporosis in women.[185]

HRT regimens and formulations vary; consult local guidelines for guidance on selecting an appropriate regimen.

Plus – calcium and vitamin D supplementation

Back

Plus –

calcium and vitamin D supplementation

Treatment recommended for ALL patients in selected patient group

Patient tolerance determines calcium formulation given.

Adverse effects of calcium supplements are primarily gastrointestinal and include increased moderate to severe constipation, bloating, and wind.[35] Nephrolithiasis may also occur.[35]

Primary options

ergocalciferol: 700-800 units orally once daily

and

calcium: adults 51-70 years of age: 1200 mg/day orally

Consider – exercise

Back

Consider –

exercise

Additional treatment recommended for SOME patients in selected patient group

3rd line – conjugated oestrogens/bazedoxifene

Back

3rd line –

conjugated oestrogens/bazedoxifene

Conjugated oestrogens/bazedoxifene are recommended only for postmenopausal women who still have a uterus.[62][70]

The Bone Health and Osteoporosis Foundation recommends conjugated oestrogens/bazedoxifene for the prevention of osteoporosis in women at significant risk of osteoporosis and only after careful consideration of alternative treatments that do not contain oestrogen.[62]

This treatment should only be used for the shortest duration consistent with treatment goals and risks for the individual woman.[62]

Adverse effects include muscle spasms, nausea, diarrhoea, dyspepsia, upper abdominal pain, oropharyngeal pain, dizziness, and neck pain.[62]

Primary options

oestrogens, conjugated/bazedoxifene: 0.45 mg/20 mg (1 tablet) orally once daily

Plus – calcium and vitamin D supplementation

Back

Plus –

calcium and vitamin D supplementation

Treatment recommended for ALL patients in selected patient group

Patient tolerance determines calcium formulation given.

Adverse effects of calcium supplements are primarily gastrointestinal and include increased moderate to severe constipation, bloating, and wind.[35] Nephrolithiasis may also occur.[35]

Primary options

ergocalciferol: 700-800 units orally once daily

and

calcium: adults 51-70 years of age: 1200 mg/day orally

Consider – exercise

Back

Consider –

exercise

Additional treatment recommended for SOME patients in selected patient group

not glucocorticoid-induced: men

fragility fracture or DXA T-score ≤-2.5 or osteopenia and at high to very high risk of fracture

1st line – bisphosphonate

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1st line –

bisphosphonate

Men aged 50 years and older presenting with any of the following should be considered for osteoporosis treatment: a hip or vertebral fracture (clinically apparent or found on vertebral imaging) regardless of T-score; fracture of the pelvis, proximal humerus, or distal forearm in a person with low bone mass or osteopenia; T-score ≤-2.5 at the femoral neck, total hip, lumbar spine, or 33% radius; high fracture risk and need for pharmacologic intervention as indicated by T-score between -1.0 and -2.5 at the femoral neck or total hip and a 10-year probability of a hip fracture ≥3% or a 10-year probability of a major osteoporosis-related fracture ≥20% (based on the Fracture Risk Assessment Tool [FRAX]).[62]

Oral bisphosphonates are the preferred first-line treatment for men with osteoporosis and a high risk of fracture, with or without prior vertebral fracture.[82] In men with a very high risk of fracture, initial treatment with an anabolic agent may be preferred.[81][82] Alendronic acid, risedronate, and zoledronic acid are approved for the treatment of osteoporosis in men. However, despite significant understanding of the pathogenesis and management of male osteoporosis, several key issues remain unresolved. It should be noted that the US Food and Drug Administration (FDA) has not approved the use of zoledronic acid for men with osteoporosis and testosterone deficiency.

The American College of Physicians guideline indicates that the response to bisphosphonate and denosumab treatment is similar in men as well as in women.[67]

A multicentre, double-blind, placebo-controlled trial of men with primary and hypogonadism-associated osteoporosis aged 50-85 years found that an intravenous infusion with zoledronic acid at baseline and 12 months reduces the risk of new morphometric vertebral fracture by 67% over a 24-month period compared with placebo.[186]

Oral bisphosphonates must be taken in the morning on an empty stomach with at least 240 mL (8 oz) of water and at least 30 minutes before eating as food decreases absorption. Patient should remain upright when taking the drug.

Primary options

alendronic acid: 10 mg orally once daily; or 70 mg orally once weekly

risedronate sodium: 35 mg orally once weekly

zoledronic acid: 5 mg intravenously once annually

Plus – calcium and vitamin D supplementation

Back

Plus –

calcium and vitamin D supplementation

Treatment recommended for ALL patients in selected patient group

Patient tolerance determines calcium formulation given.

Adverse effects of calcium supplements are primarily gastrointestinal and include increased moderate to severe constipation, bloating, and wind.[35] Nephrolithiasis may also occur.[35]

Primary options

ergocalciferol: 700-800 units orally once daily

and

calcium: adults ≤70 years of age: 1000 mg/day orally; adults >70 years of age: 1200 mg/day orally

Consider – testosterone

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Consider –

testosterone

Additional treatment recommended for SOME patients in selected patient group

Testosterone deficiency has been associated with decreased bone mineral density (BMD) in men, but evidence that testosterone replacement therapy improves BMD or reduces the risk of fractures is limited and inconsistent.[82]

One systematic review concluded that testosterone therapy did not increase BMD in the spine, femoral neck, Ward’s triangle, and the whole body, with the exception of the trochanter and total hip in older men.[187]

Testosterone therapy may be considered as an adjunct to osteoporosis-specific therapy in patients with symptomatic testosterone deficiency.[82][188] It is not recommended for men with normal testosterone levels.

There are various forms of testosterone replacement therapy available; consult your local drug formulary for available formulations and doses.

Consider – exercise

Back

Consider –

exercise

Additional treatment recommended for SOME patients in selected patient group

Evidence from systematic reviews has demonstrated that patients with osteoporosis may safely participate in exercise programmes, and that exercise may improve bone mineral density (BMD), and reduce the risk of falls.[100][101][102][103] However, the exact type of activity and its intensity, duration, and frequency are still unclear.[101][104][105][106] Supervised exercise programmes may reduce the risk of fractures more effectively.[107]

1st line – anabolic agent

Back

1st line –

anabolic agent

Guidelines recommend considering initial treatment with an anabolic agent (e.g., teriparatide, abaloparatide, romosozumab) for men with a very high risk of fractures.[81][82] However, although the American College of Physicians guideline recommends this approach for women with a very high risk of fractures, they concluded that evidence was insufficient to make a similar recommendation for men.[67]

Guidelines suggest initial treatment with an anabolic agent may be most beneficial for patients with a very high risk of fractures in practice, and they are not typically used as initial therapy in patients with a high risk of fractures.[81][99][157]

Teriparatide and abaloparatide are approved for men with a high fracture risk.[189] Abaloparatide significantly increases bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck compared with placebo in men with osteoporosis.[190][191] European guidelines for osteoporosis in men concluded that evidence of BMD improvement is strongest for abaloparatide.[82]

In the UK, teriparatide is recommended as an alternative treatment option for the secondary prevention of osteoporotic fractures in men.[192]

Randomised controlled trials in men with osteoporosis report that teriparatide increases BMD at the spine and femoral neck.[193] Although BMD gradually decreases after discontinuation of treatment, when followed by antiresorptive treatment, teriparatide decreases the risk of moderate and severe vertebral fracture.[194]

Evidence also suggests that teriparatide is as effective in men as in postmenopausal women to treat osteoporosis.[195]

Romosozumab is not approved for use in men with osteoporosis in the US or Europe, but it is approved in some other countries to treat men with osteoporosis at high risk of fracture.[62] Romosozumab treatment for 12 months resulted in significantly higher BMD at the spine, femoral neck, and total hip compared with placebo, and was well tolerated in men with osteoporosis.[196]

Primary options

abaloparatide: 80 micrograms subcutaneously once daily

teriparatide: 20 micrograms subcutaneously once daily

romosozumab: 210 mg subcutaneously once monthly for 12 months

Plus – sequential therapy

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Plus –

sequential therapy

Treatment recommended for ALL patients in selected patient group

Treatment with an anabolic agent should be followed by sequential therapy with an antiresorptive agent.[82] When treatment with teriparatide or abaloparatide is stopped, bone loss can be rapid and alternative agents should be considered to maintain bone mineral density (BMD).[62][82] When followed by antiresorptive treatment, teriparatide decreases the risk of moderate and severe vertebral fracture in men with osteoporosis.[194]

Plus – calcium and vitamin D supplementation

Back

Plus –

calcium and vitamin D supplementation

Treatment recommended for ALL patients in selected patient group

Patient tolerance determines calcium formulation given.

Adverse effects of calcium supplements are primarily gastrointestinal and include increased moderate to severe constipation, bloating, and wind.[35] Nephrolithiasis may also occur.[35]

Primary options

ergocalciferol: 700-800 units orally once daily

and

calcium: adults ≤70 years of age: 1000 mg/day orally; adults >70 years of age: 1200 mg/day orally

Consider – exercise

Back

Consider –

exercise

Additional treatment recommended for SOME patients in selected patient group

bisphosphonate or anabolic agent not tolerated or contraindicated

1st line – denosumab

Back

1st line –

denosumab

Denosumab is approved for the treatment of men with osteoporosis who are at high risk of fractures, defined as a history of fragility factors, or multiple risk factors for fractures; or those who failed or are intolerant to other available osteoporosis drug regimens.

The US Food and Drug Administration (FDA) has warned of an increased risk of severe hypocalcaemia in patients with advanced chronic kidney disease who are receiving denosumab.[141] Two safety studies showed a significant increase in the risk of severe hypocalcaemia in patients treated with denosumab compared with those treated with bisphosphonates, with the highest risk reported in patients with advanced kidney disease, particularly those on dialysis.[141][142] Severe hypocalcaemia was more common in those with mineral and bone disorder. Patients with advanced chronic kidney disease taking denosumab are at risk of serious outcomes from severe hypocalcaemia, including hospitalisation and death. Before prescribing denosumab, healthcare professionals should assess kidney function and calcium levels, and consider other treatment options for patients at risk. During treatment, frequent monitoring and prompt management of hypocalcaemia are essential.

It is also approved for osteoporosis prophylaxis in men at high risk for fracture after receiving androgen deprivation therapy for non-metastatic prostate cancer. In men with non-metastatic prostate cancer, denosumab also reduced the incidence of vertebral fracture.[197]

Primary options

denosumab: 60 mg subcutaneously every 6 months

Plus – sequential therapy

Back

Plus –

sequential therapy

Treatment recommended for ALL patients in selected patient group

Denosumab treatment should not be delayed or stopped without subsequent antiresorptive therapy or other therapy administered to prevent a rebound in bone turnover and to decrease the risk of rapid bone mineral density (BMD) loss and an increased risk of fracture.[70][108]

Plus – calcium and vitamin D supplementation

Back

Plus –

calcium and vitamin D supplementation

Treatment recommended for ALL patients in selected patient group

Patient tolerance determines calcium formulation given.

Adverse effects of calcium supplements are primarily gastrointestinal and include increased moderate to severe constipation, bloating, and wind.[35] Nephrolithiasis may also occur.[35]

Primary options

ergocalciferol: 700-800 units orally once daily

and

calcium: adults ≤70 years of age: 1000 mg/day orally; adults >70 years of age: 1200 mg/day orally

Consider – exercise

Back

Consider –

exercise

Additional treatment recommended for SOME patients in selected patient group

glucocorticoid-induced

any age: low risk of fracture

1st line – calcium and vitamin D supplementation

Back

1st line –

calcium and vitamin D supplementation

The American College of Rheumatology (ACR) recommends all adults taking prednisolone at a dose of ≥2.5 mg/day for ≥3 months should optimise calcium and vitamin D intake (with supplementation if needed) and make lifestyle modifications (e.g., balanced diet, maintaining weight in the recommended range, smoking cessation, regular weight‐bearing or resistance training exercise, limiting alcohol intake to 1-2 alcoholic beverages/day).[87] For adults with a low risk of fracture, no further treatment is recommended.[87]

Patient tolerance determines calcium formulation given.

Adverse effects of calcium supplements are primarily gastrointestinal and include increased moderate to severe constipation, bloating, and wind.[35] Nephrolithiasis may also occur.[35]

Primary options

ergocalciferol: 700-800 units orally once daily

and

calcium: adults ≤70 years of age: 1000 mg/day orally; adults >70 years of age: 1200 mg/day orally

Consider – exercise

Back

Consider –

exercise

Additional treatment recommended for SOME patients in selected patient group

<40 years of age: moderate to very high risk of fracture

1st line – bisphosphonate or denosumab or parathyroid hormone analogue

Back

1st line –

bisphosphonate or denosumab or parathyroid hormone analogue

Bisphosphonates should considered for most patients with corticosteroid treatment continuing >3 months, receiving from 2.5 to ≥7.5 mg/day of prednisolone, and in those with a history of prior fracture.[24][66]

Denosumab and parathyroid hormone analogues (e.g., teriparatide, abaloparatide) are alternative options, but both require sequential therapy.[24][199]

The American College of Rheumatology (ACR) recommends oral or intravenous bisphosphonates, a parathyroid hormone analogue, or denosumab for treatment of adults aged <40 years who are receiving long-term corticosteroids.[87] The ACR guideline emphasises shared decision-making for choice of initial therapy, considering clinician and patient preferences and comorbidities.[87]

Patients with chronic kidney disease (eGFR <35 mL/minute) should generally not be treated with bisphosphonates.[87] For women of childbearing age who are not planning a pregnancy during osteoporosis treatment, an oral or intravenous bisphosphonate is recommended, but should be used with caution due to potential adverse effects to fetal bones.[87] The bisphosphonates alendronic acid and risedronate have been shown to effectively reduce bone fracture for patients with corticosteroid induced osteoporosis.[198] [ ] [Evidence A]

Denosumab should be used with caution in women of child-bearing age due to potential adverse effects for the fetus, pregnancy should be avoided until 5 months after the last dose.[87] Denosumab treatment should be avoided when treating young adults with open growth plates.[87] Denosumab should be used with caution in patients with pre-existing hypocalcaemia or who are at high risk of hypocalcaemia (vitamin D deficient), and in patients with severe renal disease, including end-stage renal disease.[62][108] The US Food and Drug Administration (FDA) has warned of an increased risk of severe hypocalcaemia in patients with advanced chronic kidney disease who are receiving denosumab.[141] Two safety studies showed a significant increase in the risk of severe hypocalcaemia in patients treated with denosumab compared with those treated with bisphosphonates, with the highest risk reported in patients with advanced kidney disease, particularly those on dialysis.[141][142] Severe hypocalcaemia was more common in those with a mineral and bone disorder. Patients with advanced chronic kidney disease taking denosumab are at risk of serious outcomes from severe hypocalcaemia, including hospitalisation and death. Before prescribing denosumab, healthcare professionals should assess kidney function and calcium levels, and consider other treatment options for patients at risk. During treatment, frequent monitoring and prompt management of hypocalcaemia are essential.

Parathyroid hormone analogues should be avoided for the treatment of young adults with open growth plates. Teriparatide treatment has been demonstrated to increase BMD of the lumbar vertebrae compared with denosumab, and reduces the risk of vertebral fracture compared with bisphosphonates for patients with corticosteroid induced osteoporosis.[200] Preclinical and animal trials suggest that abaloparatide may mitigate or prevent bone loss from glucocorticoids and improve fracture healing.[201] There are no available data on the evaluation of abaloparatide for the treatment of corticosteroid-induced osteoporosis from clinical trials.

Primary options

alendronic acid: 10 mg orally once daily; or 70 mg orally once weekly

risedronate sodium: 5 mg orally once daily

zoledronic acid: 5 mg intravenously once annually

Secondary options

denosumab: 60 mg subcutaneously once every 6 months

Tertiary options

teriparatide: 20 micrograms subcutaneously once daily

abaloparatide: 80 micrograms subcutaneously once daily

Plus – calcium and vitamin D supplementation

Back

Plus –

calcium and vitamin D supplementation

Treatment recommended for ALL patients in selected patient group

Patient tolerance determines calcium formulation given.

Adverse effects of calcium supplements are primarily gastrointestinal and include increased moderate to severe constipation, bloating, and wind.[35] Nephrolithiasis may also occur.[35]

Primary options

ergocalciferol: 700-800 units orally once daily

and

calcium: adults ≤70 years of age: 1000 mg/day orally; adults >70 years of age: 1200 mg/day orally

Consider – sequential therapy

Back

Consider –

sequential therapy

Additional treatment recommended for SOME patients in selected patient group

No sequential therapy is needed for patients treated with oral or intravenous bisphosphonates. Patients treated with either a parathyroid hormone analogue or denosumab will need sequential therapy to prevent bone loss.[87]

Patients treated with a parathyroid hormone analogue who have a low to moderate risk of fracture when parathyroid hormone analogue treatment and corticosteroids are discontinued should receive sequential therapy with oral or intravenous bisphosphonates.[87] If a fracture occurs when the patient has been treated with a parathyroid hormone analogue for ≥12 months, sequential therapy may include oral or intravenous bisphosphonates or denosumab.[87]

If treated with denosumab sequential therapy, patients will require additional therapy with bisphosphonates 6-7 months after the last dose of denosumab, as discontinuation of denosumab after two or more doses has been associated with rapid bone loss and development of new vertebral compression fractures as soon as 7-9 months after the last dose.[87]

Patients treated with denosumab with a low to moderate risk of fracture when denosumab and corticosteroid therapy are stopped should receive 1-2 years of sequential therapy with a bisphosphonate.[87] If a fracture occurs when the patient has been treated with denosumab ≥12 months, sequential therapy may include oral or intravenous bisphosphonates or romosozumab.[87]

Consider – exercise

Back

Consider –

exercise

Additional treatment recommended for SOME patients in selected patient group

≥40 years of age: moderate risk of fracture

1st line – bisphosphonate or denosumab or parathyroid hormone analogue

Back

1st line –

bisphosphonate or denosumab or parathyroid hormone analogue

Bisphosphonates should be given to most patients with corticosteroid treatment continuing >3 months, receiving from 2.5 to ≥7.5 mg/day of prednisolone, and in those with a history of prior fracture.[24][66]

Denosumab and parathyroid hormone analogues (e.g., teriparatide, abaloparatide) are alternative options, but both require sequential therapy.[24][199] The American College of Rheumatology (ACR) recommends oral or intravenous bisphosphonates, denosumab, or a parathyroid hormone analogue for treatment of adults aged ≥40 years at moderate risk of fracture who are receiving long-term corticosteroids, with no preference between these agents.[87] The ACR guideline emphasises shared decision-making for choice of initial therapy, considering clinician and patient preferences and comorbidities.[87]

Teriparatide treatment has been demonstrated to increase BMD of the lumbar vertebrae compared with denosumab, and reduces the risk of vertebral fracture compared with bisphosphonates for patients with corticosteroid induced osteoporosis.[200] Preclinical and animal trials suggest that abaloparatide may mitigate or prevent bone loss from glucocorticoids and improve fracture healing.[201] There are no available data on the evaluation of abaloparatide for the treatment of corticosteroid-induced osteoporosis from clinical trials.

Primary options

alendronic acid: 10 mg orally once daily; or 70 mg orally once weekly

risedronate sodium: 5 mg orally once daily

zoledronic acid: 5 mg intravenously once annually

Secondary options

denosumab: 60 mg subcutaneously once every 6 months

Tertiary options

teriparatide: 20 micrograms subcutaneously once daily

abaloparatide: 80 micrograms subcutaneously once daily

Plus – calcium and vitamin D supplementation

Back

Plus –

calcium and vitamin D supplementation

Treatment recommended for ALL patients in selected patient group

Patient tolerance determines calcium formulation given.

Adverse effects of calcium supplements are primarily gastrointestinal and include increased moderate to severe constipation, bloating, and wind.[35] Nephrolithiasis may also occur.[35]

Primary options

ergocalciferol: 700-800 units orally once daily

and

calcium: adults ≤70 years of age: 1000 mg/day orally; adults >70 years of age: 1200 mg/day orally

Consider – sequential therapy

Back

Consider –

sequential therapy

Additional treatment recommended for SOME patients in selected patient group

Patients treated with a parathyroid hormone analogue who have a low to moderate risk of fracture when parathyroid hormone analogue treatment and corticosteroids are discontinued should receive sequential therapy with oral or intravenous bisphosphonates.[87] If a fracture occurs when the patients has been treated with a parathyroid hormone analogue for ≥12 months, sequential therapy may include oral or intravenous bisphosphonates or denosumab.[87]

Consider – exercise

Back

Consider –

exercise

Additional treatment recommended for SOME patients in selected patient group

2nd line – raloxifene or romosozumab

Back

2nd line –

raloxifene or romosozumab

In spite of a lack of evidence on the effectiveness of raloxifene or romosozumab for patients with corticosteroid induced osteoporosis, the American College of Rheumatology (ACR) conditionally recommends raloxifene or romosozumab as a treatment for adults aged ≥40 years at moderate risk of fracture, including those taking a high dose of corticosteroids (initial prednisolone dose ≥30 mg/day or cumulative prednisolone dose ≥5 g in 1 year) only if they are intolerant of all other treatments.[87][203][204]

Adverse effects may include an increased risk of venous thromboembolism, myocardial infarction, stroke, or death.[87]

Primary options

raloxifene: 60 mg orally once daily

romosozumab: 210 mg subcutaneously once monthly for 12 months

Plus – calcium and vitamin D supplementation

Back

Plus –

calcium and vitamin D supplementation

Treatment recommended for ALL patients in selected patient group

Patient tolerance determines calcium formulation given.

Adverse effects of calcium supplements are primarily gastrointestinal and include increased moderate to severe constipation, bloating, and wind.[35] Nephrolithiasis may also occur.[35]

Primary options

ergocalciferol: 700-800 units orally once daily

and

calcium: adults ≤70 years of age: 1000 mg/day orally; adults >70 years of age: 1200 mg/day orally

Consider – sequential therapy

Back

Consider –

sequential therapy

Additional treatment recommended for SOME patients in selected patient group

Patients treated with raloxifene who are at a low or moderate risk of fracture when raloxifene and corticosteroid treatment is stopped will not require sequential therapy.[87] If a new fracture occurs in patients treated with raloxifene for ≥12 months, sequential therapy with oral or intravenous bisphosphonates is needed.[87]

Patients treated with romosozumab who are at a low or moderate risk of fracture when romosozumab and corticosteroid treatment is stopped will need sequential therapy with oral or intravenous bisphosphonate, for those who experience a new fracture after ≥12 months of romosozumab treatment, oral or intravenous bisphosphonate or denosumab can be used for sequential therapy.[87] However, patients treated with denosumab for sequential therapy will require a further 6-7 months of bisphosphonate therapy to prevent rapid bone loss and the development of new vertebral compression fractures.

Consider – exercise

Back

Consider –

exercise

Additional treatment recommended for SOME patients in selected patient group

Evidence from systematic reviews has demonstrated that patients with osteoporosis may safely participate in exercise programmes, and that exercise may improve bone mineral density (BMD) and reduce the risk of falls.[100][101][102][103][106] However, the exact type of activity and its intensity, duration, and frequency are still unclear.[100][101][104][106]

≥40 years of age: high risk of fracture

1st line – parathyroid hormone analogue or denosumab

Back

1st line –

parathyroid hormone analogue or denosumab

The American College of Rheumatology (ACR) recommends a parathyroid hormone analogue (e.g., teriparatide, abaloparatide) for the treatment of adults ≥40 years with high risk of fracture including patients on very high-dose corticosteroid treatment (initial prednisolone dose ≥30 mg/day or cumulative prednisolone dose ≥5 g in 1 year).[87] Teriparatide treatment has been demonstrated to increase BMD of the lumbar vertebrae compared with denosumab, and reduces the risk of vertebral fracture compared with bisphosphonates for patients with corticosteroid induced osteoporosis.[200]

Preclinical and animal trials suggest that abaloparatide may mitigate or prevent bone loss from glucocorticoids and improve fracture healing.[201] There are no available data on the evaluation of abaloparatide for the treatment of corticosteroid-induced osteoporosis from clinical trials.

Denosumab may be used for the treatment of adults ≥40 years at high risk of fracture when a parathyroid hormone analogue is not appropriate.[87] One systematic review reported that denosumab significantly increased BMD in the lumbar spine at 6 months, and in the lumbar spine and femoral neck at 12 months, compared with bisphosphonate therapy in patients with corticosteroid-induced osteoporosis.[202]

Denosumab should be used with caution in women of child-bearing age due to potential adverse effects for the fetus, pregnancy should be avoided until 5 months after the last dose.[87] Denosumab should be used with caution in patients with pre-existing hypocalcaemia or who are at high risk of hypocalcaemia (vitamin D deficient), and in patients with severe renal disease, including end-stage renal disease.[62][108] The US Food and Drug Administration (FDA) has warned of an increased risk of severe hypocalcaemia in patients with advanced chronic kidney disease who are receiving denosumab.[141] Two safety studies showed a significant increase in the risk of severe hypocalcaemia in patients treated with denosumab compared with those treated with bisphosphonates, with the highest risk reported in patients with advanced kidney disease, particularly those on dialysis.[141][142] Severe hypocalcaemia was more common in those with a mineral and bone disorder. Patients with advanced chronic kidney disease taking denosumab are at risk of serious outcomes from severe hypocalcaemia, including hospitalisation and death. Before prescribing denosumab, healthcare professionals should assess kidney function and calcium levels, and consider other treatment options for patients at risk. During treatment, frequent monitoring and prompt management of hypocalcaemia are essential.

Primary options

teriparatide: 20 micrograms subcutaneously once daily

abaloparatide: 80 micrograms subcutaneously once daily

Secondary options

denosumab: 60 mg subcutaneously once every 6 months

Plus – calcium and vitamin D supplementation

Back

Plus –

calcium and vitamin D supplementation

Treatment recommended for ALL patients in selected patient group

Patient tolerance determines calcium formulation given.

Adverse effects of calcium supplements are primarily gastrointestinal and include increased moderate to severe constipation, bloating, and wind.[35] Nephrolithiasis may also occur.[35]

Primary options

ergocalciferol: 700-800 units orally once daily

and

calcium: adults ≤70 years of age: 1000 mg/day orally; adults >70 years of age: 1200 mg/day orally

Consider – sequential therapy

Back

Consider –

sequential therapy

Additional treatment recommended for SOME patients in selected patient group

Patients treated with a parathyroid hormone analogue should receive sequential therapy with oral or intravenous bisphosphonates if they have a low to moderate risk of fracture when the parathyroid hormone analogue and corticosteroids are discontinued.[87] If a fracture occurs when the patients has been treated with a parathyroid hormone analogue for ≥12 months, sequential therapy may include oral or intravenous bisphosphonates or denosumab.[87]

Patients initially treated with denosumab with a low to moderate risk of fracture when denosumab and corticosteroid therapy are stopped should receive 1-2 years of sequential therapy with bisphosphonate to prevent rapid bone loss.[87] If a fracture occurs when the patients has been treated with denosumab ≥12 months, sequential therapy may include oral or intravenous bisphosphonates or romosozumab.[87]

Consider – exercise

Back

Consider –

exercise

Additional treatment recommended for SOME patients in selected patient group

2nd line – bisphosphonate

Back

2nd line –

bisphosphonate

An oral or intravenous bisphosphonate is recommended as a second-line treatment for patients ≥40 years with a high risk of fracture, based on evidence of superior BMD improvements with parathyroid hormone analogues and denosumab.[87]

The bisphosphonates alendronic acid and risedronate have been shown to effectively reduce bone fracture for patients with corticosteroid induced osteoporosis.[198] [ ] [Evidence A]

Primary options

alendronic acid: 10 mg orally once daily; or 70 mg orally once weekly

risedronate sodium: 5 mg orally once daily

zoledronic acid: 5 mg intravenously once annually

Plus – calcium and vitamin D supplementation

Back

Plus –

calcium and vitamin D supplementation

Treatment recommended for ALL patients in selected patient group

Patient tolerance determines calcium formulation given.

Adverse effects of calcium supplements are primarily gastrointestinal and include increased moderate to severe constipation, bloating, and wind.[35] Nephrolithiasis may also occur.[35]

Primary options

ergocalciferol: 700-800 units orally once daily

and

calcium: adults ≤70 years of age: 1000 mg/day orally; adults >70 years of age: 1200 mg/day orally

Consider – sequential therapy

Back

Consider –

sequential therapy

Additional treatment recommended for SOME patients in selected patient group

Patients treated with oral or intravenous bisphosphonates who have a low to moderate risk of fracture and discontinue corticosteroid treatment do not require sequential therapy.[87] However, if a new fracture occurs after ≥12 months of initial bisphosphonate therapy, sequential therapy may include denosumab, a parathyroid hormone analogue, or romosozumab.

If treated with denosumab sequential therapy, patients will require additional therapy with bisphosphonates 6-7 months after the last dose of denosumab to prevent rapid bone loss and development of new vertebral compression fractures.[87]

Consider – exercise

Back

Consider –

exercise

Additional treatment recommended for SOME patients in selected patient group

3rd line – raloxifene or romosozumab

Back

3rd line –

raloxifene or romosozumab

In spite of a lack of evidence on the effectiveness of raloxifene or romosozumab for patients with corticosteroid induced osteoporosis, the American College of Rheumatology (ACR) conditionally recommends raloxifene or romosozumab as a treatment for adults aged ≥40 years at high risk of fracture, including those taking a high dose of corticosteroids (initial prednisolone dose ≥30 mg/day or cumulative prednisolone dose ≥5 g in 1 year) only if they are intolerant of all other treatments.[87][203][204]

Adverse effects may include an increased risk of venous thromboembolism, myocardial infarction, stroke, or death.[87]

Primary options

raloxifene: 60 mg orally once daily

romosozumab: 210 mg subcutaneously once monthly for 12 months

Plus – calcium and vitamin D supplementation

Back

Plus –

calcium and vitamin D supplementation

Treatment recommended for ALL patients in selected patient group

Patient tolerance determines calcium formulation given.

Adverse effects of calcium supplements are primarily gastrointestinal and include increased moderate to severe constipation, bloating, and wind.[35] Nephrolithiasis may also occur.[35]

Primary options

ergocalciferol: 700-800 units orally once daily

and

calcium: adults ≤70 years of age: 1000 mg/day orally; adults >70 years of age: 1200 mg/day orally

Consider – sequential therapy

Back

Consider –

sequential therapy

Additional treatment recommended for SOME patients in selected patient group

Patients treated with raloxifene who are at a low or moderate risk of fracture when raloxifene and corticosteroid treatment is stopped will not require sequential therapy.[87] If a new fracture occurs in patients treatment with raloxifene for ≥12 months, sequential therapy with oral or intravenous bisphosphonates is needed.

Patients treated with denosumab for sequential therapy will require a further 6-7 months of bisphosphonate therapy to prevent rapid bone loss and the development of new vertebral compression fractures.

Consider – exercise

Back

Consider –

exercise

Additional treatment recommended for SOME patients in selected patient group

≥40 years of age: very high risk of fracture

1st line – parathyroid hormone analogue

Back

1st line –

parathyroid hormone analogue

A parathyroid hormone analogue is recommended for adults ≥40 years with a very high risk of fracture including patients on very high-dose corticosteroids treatment (initial prednisolone dose ≥30 mg/day or cumulative prednisolone dose ≥5 g in 1 year).[87]

Teriparatide treatment has been demonstrated to increase bone mineral density (BMD) of the lumbar vertebrae compared with denosumab, and reduces the risk of vertebral fracture compared with bisphosphonates for patients with corticosteroid induced osteoporosis.[200] Preclinical and animal trials suggest that abaloparatide may mitigate or prevent bone loss from glucocorticoids and improve fracture healing.[201]

There are no available data on the evaluation of abaloparatide for the treatment of corticosteroid-induced osteoporosis from clinical trials.

Primary options

teriparatide: 20 micrograms subcutaneously once daily

abaloparatide: 80 micrograms subcutaneously once daily

Plus – calcium and vitamin D supplementation

Back

Plus –

calcium and vitamin D supplementation

Treatment recommended for ALL patients in selected patient group

Patient tolerance determines calcium formulation given.

Adverse effects of calcium supplements are primarily gastrointestinal and include increased moderate to severe constipation, bloating, and wind.[35] Nephrolithiasis may also occur.[35]

Primary options

ergocalciferol: 700-800 units orally once daily

and

calcium: adults ≤70 years of age: 1000 mg/day orally; adults >70 years of age: 1200 mg/day orally

Consider – sequential therapy

Back

Consider –

sequential therapy

Additional treatment recommended for SOME patients in selected patient group

Patients treated with a parathyroid hormone analogue should have sequential therapy of oral or intravenous bisphosphonates if they are at low to moderate risk of fracture when the parathyroid hormone analogue and corticosteroids are discontinued.[87] If a new fracture occurs when the patients has been treated with a parathyroid hormone analogue for ≥12 months, sequential therapy may include oral or intravenous bisphosphonates or denosumab.[87]

If treated with denosumab sequential therapy, patients will require additional therapy with bisphosphonates for 6-7 months after the last dose of denosumab to prevent rapid bone loss and development of new vertebral compression fractures.[87]

Consider – exercise

Back

Consider –

exercise

Additional treatment recommended for SOME patients in selected patient group

2nd line – denosumab or bisphosphonate

Back

2nd line –

denosumab or bisphosphonate

The American College of Rheumatology (ACR) recommends denosumab or a bisphosphonate for the treatment of adults ≥40 years at very high risk of fracture when a parathyroid hormone analogue is not appropriate.[87]

Denosumab and bisphosphonates should be used with caution in women of child bearing age due to potential adverse effects for the fetus, pregnancy should be avoided until 5 months after the last dose of denosumab.[87] Denosumab should be used with caution in patients with pre-existing hypocalcaemia or who are at high risk of hypocalcaemia (vitamin D deficient), and in patients with severe renal disease, including end-stage renal disease.[62][108] The US Food and Drug Administration (FDA) has warned of an increased risk of severe hypocalcaemia in patients with advanced chronic kidney disease who are receiving denosumab.[141] Two safety studies showed a significant increase in the risk of severe hypocalcaemia in patients treated with denosumab compared with those treated with bisphosphonates, with the highest risk reported in patients with advanced kidney disease, particularly those on dialysis.[141][142] Severe hypocalcaemia was more common in those with a mineral and bone disorder. Patients with advanced chronic kidney disease taking denosumab are at risk of serious outcomes from severe hypocalcaemia, including hospitalisation and death. Before prescribing denosumab, healthcare professionals should assess kidney function and calcium levels, and consider other treatment options for patients at risk. During treatment, frequent monitoring and prompt management of hypocalcaemia are essential.

One systematic review reported that denosumab significantly increased BMD in the lumbar spine at 6 months, and in the lumbar spine and femoral neck at 12 months, compared with bisphosphonate therapy in patients with corticosteroid-induced osteoporosis.[202]

The bisphosphonates alendronic acid and risedronate have been shown to effectively reduce bone fracture for patients with corticosteroid induced osteoporosis.[198] [ ] [Evidence A]

Primary options

denosumab: 60 mg subcutaneously once every 6 months

alendronic acid: 10 mg orally once daily; or 70 mg orally once weekly

risedronate sodium: 5 mg orally once daily

zoledronic acid: 5 mg intravenously once annually

Plus – calcium and vitamin D supplementation

Back

Plus –

calcium and vitamin D supplementation

Treatment recommended for ALL patients in selected patient group

Patient tolerance determines calcium formulation given.

Adverse effects of calcium supplements are primarily gastrointestinal and include increased moderate to severe constipation, bloating, and wind.[35] Nephrolithiasis may also occur.[35]

Primary options

ergocalciferol: 700-800 units orally once daily

and

calcium: adults ≤70 years of age: 1000 mg/day orally; adults >70 years of age: 1200 mg/day orally

Consider – sequential therapy

Back

Consider –

sequential therapy

Additional treatment recommended for SOME patients in selected patient group

Patients treated with denosumab with a low to moderate risk of fracture when denosumab and corticosteroid therapy are withdrawn should receive 1-2 years of sequential therapy with bisphosphonates. If a new fracture occurs when the patients has been treated with denosumab ≥12 months, sequential therapy may include oral or intravenous bisphosphonates or romosozumab.[87]

Consider – exercise

Back

Consider –

exercise

Additional treatment recommended for SOME patients in selected patient group

3rd line – raloxifene or romosozumab

Back

3rd line –

raloxifene or romosozumab

In spite of a lack of evidence on the effectiveness of raloxifene or romosozumab for patients with corticosteroid induced osteoporosis, the American College of Rheumatology (ACR) conditionally recommends raloxifene or romosozumab as a treatment for adults aged ≥40 years at a very high risk of fracture, including those taking a high dose of corticosteroids (initial prednisolone dose ≥30 mg/day or cumulative prednisolone dose ≥5 g in 1 year) only if they are intolerant of all other treatments.[87][203][204]

Adverse effects may include an increased risk of venous thromboembolism, myocardial infarction, stroke, or death.[87]

Primary options

raloxifene: 60 mg orally once daily

romosozumab: 210 mg subcutaneously once monthly for 12 months

Plus – calcium and vitamin D supplementation

Back

Plus –

calcium and vitamin D supplementation

Treatment recommended for ALL patients in selected patient group

Patient tolerance determines calcium formulation given.

Adverse effects of calcium supplements are primarily gastrointestinal and include increased moderate to severe constipation, bloating, and wind.[35] Nephrolithiasis may also occur.[35]

Primary options

ergocalciferol: 700-800 units orally once daily

and

calcium: adults ≤70 years of age: 1000 mg/day orally; adults >70 years of age: 1200 mg/day orally

Consider – sequential therapy

Back

Consider –

sequential therapy

Additional treatment recommended for SOME patients in selected patient group

Patients treated with raloxifene who are at a low or moderate risk of fracture when raloxifene and corticosteroid treatment is stopped will not require sequential therapy.[87] If a new fracture occurs in patients receiving treatment with raloxifene for ≥12 months, sequential therapy with oral or intravenous bisphosphonates is needed.

Consider – exercise

Back

Consider –

exercise

Additional treatment recommended for SOME patients in selected patient group

Use of this content is subject to our disclaimer

Osteoporosis

Treatment algorithm

not glucocorticoid-induced: women

bisphosphonate

Primary options

calcium and vitamin D supplementation

Primary options

exercise

denosumab

Primary options

sequential therapy

calcium and vitamin D supplementation

Primary options

exercise

anabolic agent

Primary options

sequential therapy

calcium and vitamin D supplementation

Primary options

exercise

selective oestrogen receptor modulator (SERM)

Primary options

calcium and vitamin D supplementation

Primary options

exercise

hormone replacement therapy (HRT)

calcium and vitamin D supplementation

Primary options

exercise

conjugated oestrogens/bazedoxifene

Primary options

calcium and vitamin D supplementation

Primary options

exercise

not glucocorticoid-induced: men

bisphosphonate

Primary options

calcium and vitamin D supplementation

Primary options

testosterone

exercise

anabolic agent

Primary options

sequential therapy

calcium and vitamin D supplementation

Primary options

exercise

denosumab

Primary options

sequential therapy

calcium and vitamin D supplementation

Primary options

exercise

glucocorticoid-induced

calcium and vitamin D supplementation

Primary options

exercise

bisphosphonate or denosumab or parathyroid hormone analogue

Primary options

Secondary options

Tertiary options

calcium and vitamin D supplementation

Primary options

sequential therapy

exercise

bisphosphonate or denosumab or parathyroid hormone analogue

Primary options

Secondary options

Tertiary options

calcium and vitamin D supplementation

Primary options

sequential therapy

exercise

raloxifene or romosozumab

Primary options

calcium and vitamin D supplementation

Primary options

sequential therapy

exercise

parathyroid hormone analogue or denosumab