Approach
The management of osteomalacia should be directed at treating the underlying etiology and correction of the hypocalcemia, vitamin D deficiency, and hypophosphatemia.
All patients should maintain an adequate elemental calcium intake according to local guidelines, as inadequate calcium intake may contribute to the development of osteomalacia.
Calcium and vitamin D deficiency
The mainstay of treatment is the provision of adequate calcium and vitamin D to correct the causative deficiency. Typically, vitamin D supplementation leads to dramatic improvements in muscle strength and a reduction of bone tenderness within weeks of initiation. The serum calcium concentration, 25-hydroxyvitamin D concentration, urinary calcium excretion, and bone density should be monitored during treatment to assess for clinical improvement and potential over-treatment.
Patients who have intestinal malabsorption with a history of gastrectomy, small bowel disease, bariatric surgery, or resection usually do not respond adequately to small doses of vitamin D replacement. In the presence of steatorrhea, daily dose of vitamin D may need to be increased.
If the above treatments fail, vitamin D analogs (e.g., calcitriol), which are more effective, may be required. Vitamin D deficiency resulting from intestinal malabsorption syndromes is more likely to warrant this second-line therapy.[56]
Patients with concomitant renal disease or inherited disorders of vitamin D metabolism are appropriate for treatment with vitamin D analogs.
Chronic kidney disease-mineral bone disorder (CKD-MBD)
The medical management of CKD-MBD (previously known as renal osteodystrophy) includes the maintenance of normal calcium and phosphate levels, treatment with calcitriol and phosphate-binding agents, and avoidance of aluminum-containing phosphate binders.
Disorders of phosphate wasting and oncogenic osteomalacia
In patients with phosphate-wasting disorders, replacement with oral phosphate is required only in patients who are symptomatic, have very low serum phosphate levels, or have a renal tubular defect leading to chronic phosphate loss. These patients often need additional calcium and vitamin D analog supplementation.[57][58]
Plasma calcium concentration, urinary calcium excretion, and bone density are monitored while on therapy. Successful treatment of osteomalacia is likely with an increase in urinary calcium excretion and an increase in bone density by dual-energy x-ray absorptiometry.
In skeletally mature patients, the goal of therapy is to prevent symptoms of hypophosphatemia such as muscle weakness and paresthesias. For most patients, treatment of the underlying disorder causing the low phosphorus is adequate.
X-linked hypophosphatemia or oncogenic osteomalacia
Burosumab, a monoclonal antibody that increases renal tubular phosphate reabsorption and increases serum 1,25-dihydroxyvitamin D levels through inhibition of fibroblast growth factor 23 (FGF23), is approved in the US for the treatment of X-linked hypophosphatemia and FGF23-related hypophosphatemia in tumor-induced osteomalacia associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized. Burosumab is also approved for both of these indications in Europe. It is contraindicated in patients with severe renal impairment/end-stage renal disease or hyperphosphatemia, and must not be used with oral phosphate and/or active vitamin D analogs (e.g., calcitriol).
One 24-week randomized trial in symptomatic adults reported improvement in stiffness, as well as improved fracture healing compared to placebo.[59] Initial results from phase 2 trials suggest that burosumab improved serum phosphate levels in adults with tumor-induced osteomalacia.[60][61] These tumors release FGF23 which causes hypophosphatemia.
Calcium plus a vitamin D analog plus phosphate supplementation is an alternative treatment option in these patients, and may be used if burosumab is not available or contraindicated.
Special considerations
Patients taking anticonvulsant medications, glucocorticoids, or other drugs that activate steroid and xenobiotic receptors require higher doses of vitamin D. The goal is to achieve concentrations of 25-hydroxyvitamin D at about the 30-60 ng/mL (75-150 nmol/L) range.[18]
In a small prospective cohort study, it was shown that taking vitamin D with the largest meal of the day improves vitamin D absorption by 50%.[62]
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