Osteomalacia

In adults with bone pain, proximal weakness, insufficiency fractures, or suspected impaired mineralization, obtain serum phosphate, calcium, alkaline phosphatase, parathyroid hormone, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and creatinine. Obtain spot urine phosphate, creatinine, and calcium concurrently to calculate tubular maximum phosphate reabsorption per glomerular filtration rate (TmP/GFR) and urinary calcium:creatinine ratio. NatureNatureClinical practice recommendations for the diagnosis and ... - Nature

An elevated alkaline phosphatase supports active rickets or osteomalacia but is not etiologic. In adults, use bone-specific alkaline phosphatase when available because approximately half of circulating total alkaline phosphatase originates from hepatocytes. Persistently elevated alkaline phosphatase with low urinary calcium is described in undertreated hypophosphatemic rickets or osteomalacia; alkaline phosphatase usually falls and urinary calcium rises with skeletal healing. NatureNatureClinical practice recommendations for the diagnosis and ... - Nature

Very low 25-hydroxyvitamin D favors nutritional vitamin D deficiency as a mineralization defect. Osteomalacia related to vitamin D deficiency is typically associated with 25-hydroxyvitamin D concentrations below 15 to 30 nmol/L; vitamin D deficiency can cause osteomalacia, muscle weakness, and worsen osteopenia or osteoporosis. NEJM+1NEJMVitamin D Deficiency | New England Journal of MedicineWileyRickets and Osteomalacia - Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism - Wiley Online Library

Calculate TmP/GFR from paired serum and spot urine phosphate and creatinine in patients with hypophosphatemia. A low TmP/GFR documents impaired tubular phosphate reabsorption and establishes renal phosphate wasting; this is the pivotal branch point before pursuing FGF23-mediated disorders, inherited phosphate-wasting conditions, or generalized proximal tubular dysfunction. Nature+1NatureClinical practice recommendations for the diagnosis and ... - NatureWolters KluwerHypophosphatemic rickets : Indian Journal of Endocrinology and Metabolism

After renal phosphate wasting is documented, determine whether loss is isolated or occurs with other tubular solute losses. Isolated phosphate wasting is compatible with FGF23-mediated disease, whereas associated tubular losses redirect the evaluation to proximal tubular disorders. Wolters KluwerWolters KluwerHypophosphatemic rickets : Indian Journal of Endocrinology and Metabolism

Measure 1,25-dihydroxyvitamin D and FGF23 in the untreated state when possible. FGF23 physiologically increases renal phosphate wasting and suppresses active vitamin D; therefore, hypophosphatemia with low-normal 1,25-dihydroxyvitamin D is a characteristic FGF23-excess pattern. FGF23 measurements are most informative before therapy, and assay-specific reference ranges vary substantially. Nature+1NatureClinical practice recommendations for the diagnosis and ... - NatureNatureFGF23 and Phosphate Wasting Disorders | Bone Research

A lifelong history of rickets, short stature or growth failure, lower-limb deformity, dental abnormalities, or a family history supports inherited hypophosphatemic disease. The recommended clinical evaluation for X-linked hypophosphatemia includes assessment for rickets, growth failure, dental abnormalities, and craniosynostosis or intracranial hypertension, with radiologic grading of rickets or osteomalacic lesions and biochemical measurement of phosphate handling. NEJM+1NEJMBurosumab Therapy in Children with X-Linked HypophosphatemiaNatureClinical practice recommendations for the diagnosis and ... - Nature

Consider tumor-induced osteomalacia in an adult with acquired progressive bone pain, muscle weakness, fatigue, insufficiency or fragility fractures, hypophosphatemia, low TmP/GFR, elevated alkaline phosphatase, and low-normal 1,25-dihydroxyvitamin D. Tumor-induced osteomalacia is a rare paraneoplastic form of renal phosphate wasting caused by FGF23-secreting tumors, which are often small and may produce years of diagnostic delay. JAMA+2JAMATumor-Induced Osteomalacia | Geriatrics - JAMA NetworkNatureFGF23 and Phosphate Wasting Disorders | Bone ResearchNatureTumour-induced osteomalacia | Nature Reviews Disease Primers

The key clinical consequence of recognizing tumor-induced osteomalacia is potential cure: complete excision of the responsible tumor is associated with dramatic symptomatic improvement and correction of metabolic abnormalities. Once the biochemical phenotype supports acquired FGF23 excess, shift the workup from empiric supplementation alone to localization and definitive tumor-directed treatment. NatureNatureFGF23 and Phosphate Wasting Disorders | Bone Research

For nutritional osteomalacia, correct the documented vitamin D and calcium deficit and address the source of deficiency, including malabsorption when present. Nutritional osteomalacia may respond to low doses of calcium and vitamin D, whereas vitamin D deficiency rickets is described as responsive to small vitamin D doses; regimen selection and monitoring should be individualized because the cited literature does not provide a universal adult dosing protocol. WileyWileyRickets and Osteomalacia - Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism - Wiley Online Library

For FGF23-mediated hypophosphatemia, conventional management has used oral phosphate with active vitamin D analogs. This approach may be limited by gastrointestinal intolerance and renal toxicity, can increase FGF23 concentrations, and often does not normalize serum phosphate, leaving persistent skeletal risk. NatureNatureA phase 2 trial of burosumab for treatment of fibroblast growth factor-23-mediated hypophosphatemia in children and adults with fibrous dysplasia | Bone Research

Burosumab is a monoclonal antibody against FGF23 and is approved for X-linked hypophosphatemia and tumor-induced osteomalacia. It provides a targeted option when these diagnoses are established, including tumor-induced osteomalacia in which a tumor cannot be identified or cannot be definitively treated; its use should be paired with serial biochemical and skeletal assessment. Oxford Academic+2Oxford AcademicBurosumab, a Transformational Treatment in a Pediatric Patient With ...Oxford AcademicBurosumab use in fibroblast growth factor-23-mediated ...Oxford AcademicBurosumab treatment for fibroblast growth factor-23-associated ...

Obtain radiologic evaluation to identify and grade osteomalacic lesions when the diagnosis is suspected or disease activity must be established. In an adult with biochemical FGF23-mediated phosphate wasting and no childhood phenotype, use the imaging strategy to support localization of an occult phosphaturic tumor rather than to merely document fractures. Nature+2NatureClinical practice recommendations for the diagnosis and ... - NatureNatureFGF23 and Phosphate Wasting Disorders | Bone ResearchNatureTumour-induced osteomalacia | Nature Reviews Disease Primers

Refer patients with suspected tumor-induced osteomalacia for coordinated endocrine, metabolic bone, and tumor-localization evaluation because complete lesion excision is the intervention linked to correction of the syndrome. Thermal ablation has been reported as a treatment approach for tumor-induced osteomalacia, but complete excision remains the documented curative mechanism in the cited clinical literature. Nature+1NatureFGF23 and Phosphate Wasting Disorders | Bone ResearchOxford AcademicThermal Ablation for Treating Tumor-induced Osteomalacia in a ...

Escalate promptly when progressive weakness, multiple fragility fractures, height loss, or persistent biochemical phosphate wasting is present. These findings are described in delayed tumor-induced osteomalacia and signal ongoing mineralization failure rather than uncomplicated low bone density. NatureNatureFGF23 and Phosphate Wasting Disorders | Bone Research