Endocrine Abstracts

Chronic hypophosphatemia (HP) can be observed among patients (pts) evaluated and treated for osteoporosis, but its prevalence and management are poorly defined. In this study we analyze prevalence, clinical features and diagnostic workup for chronic HP among pts attending a third-level osteoporosis office. Chronic HP was defined as serum phosphate levels persistently < 2.7 mg/dl over a period ≥ 6 months. Tubular reabsorption of phosphate (TRP) was measured and, in presence of renal wasting, serum FGF23 was required (DIASORIN; normal values 23.2–95.4 pg/ml). When non-suppressed FGF23 levels were detected, a diagnosis of Tumour Induced Osteomalacia (TIO) was considered. Positive family history for bone diseases, hyperparathyroidism, vitamin D deficiency, and interfering drugs were excluded. Among 2055 pts followed from January 2017 to December 2018, nineteen were diagnosed with chronic HP due to renal wasting (0.92%). Circulating FGF23 measurement helped distinguish FGF23-independent renal wasting (2 pts, both diagnosed with Fanconi’s syndrome; FGF23 levels: 5 pg/ml and 18.5 pg/ml, respectively), from FGF23-dependent forms (n=17; median FGF23 level: 52 pg/ml, range 35–103). Among the latter cases, one patient had a clinical diagnosis of hypophosphatemic rickets, though any mutation of the PHEX gene could be detected. The remaining 16 pts (12 females) had no osteomalacia or muscle symptoms, while 7 out of 16 (44%) had a history of fragility fractures. On anti-osteoporotic treatment (bisphosphonates or denosumab), these pts showed poor bone mineral density (BMD) improvement and serum alkaline phosphatase levels remained above the first tertile of normal range in half of them. ⁶⁸Ga-DOTATOC-PET was carried out in 8 pts; it identified suspicious lesions associated with increased uptake only in 4 of them (50%). Pts with positive PET had the lowest phosphate levels (median 2.25, range 1.6–2.5 mg/dl), the highest FGF23 levels (median 70.5, range 48–84 pg/ml), the lowest BMD values and the worst responses to anti-osteoporotic treatments. Following imaging and histologic studies, one meningioma and one paraganglioma were identified; two other patients with thyroid and left inguinal uptakes, respectively, are waiting to complete diagnostic workup. In conclusion, prevalence of chronic HP is nearly 1% among osteoporotic pts, but clinical management is challenging. Mild asymptomatic HP can be associated with normal or only slightly elevated FGF23 levels and negative ⁶⁸Ga-PET. Nonetheless, chronic HP can affect bone metabolism and efficacy of anti-osteoporotic treatments.