Endocrine Abstracts

Phosphorus is involved in energy storage, metabolism, nucleic acids, cell membrane function, cell signaling; it is a fundamental constituent of skeleton and teeth. Pi homeostasis is regulated mainly by three hormones, namely parathyroid hormone (PTH), vitamin D and Fibroblast Growth Factor 23 (FGF23). Additionally, sex hormones are known to decrease circulating Pi levels, by reducing renal tubular reabsorption through direct and indirect effects on renal phosphate channels and likely stimulating FGF23 release. Though some patients may complain of muscle weakness, mild hypophosphatemia (HP) is usually asymptomatic, and, consequently, often overlooked, so that its prevalence in the general population is not known. Indeed, HP is not a rare feature in patients with osteoporosis. On the other hand, severe and chronic HP causes muscle weakness, bone pain and deformity, fragility fractures (osteomalacia), rhabdomyolysis, impaired mental status, heart failure. Several mechanisms can be involved, and reduced Pi intestinal absorption, internal redistribution or urinary loss must be differentiated. Once urinary loss has been established, differential diagnosis includes FGF23-dependent conditions [renal transplantation, tumor induced osteomalacia (TIO), hereditary hypophosphatemic rickets] and FGF23-independent ones (primary and secondary hyperparathyroidism, renal tubular defects, diuretics, glucocorticoid therapy, hereditary hypophosphatemic rickets with hypercalciuria). Diagnostic workup is complex and often unrewarding, and the cause of chronic HP can remain unexplained in a number of patients. Finally, in patients affected with osteoporosis, HP may occur as an adverse effect of the anti-osteoporotic drugs (bisphosphonates, denosumab, teriparatide), though most studies show that HP is rare and generally self-limiting in this context. Indeed, a subset of osteoporotic patients developing chronic HP on anti-osteoporotic treatment can be observed in clinical practice, but frequency and implications of this condition are not known. Lastly, it should be considered that recently a specific anti-FGF23 treatment is available implying the need to correctly diagnose FGF23-related HP.