Long-term use of burosumab for the treatment of tumor-induced osteomalacia.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by tumoral overproduction of FGF-23. Due to local recurrence, we describe the long-term efficacy and safety profile of burosumab, an anti-FGF-23 monoclonal antibody, in a TIO patient after three unsuccessfully surgical attempts. INTRODUCTION: TIO is a rare paraneoplastic syndrome caused by tumoral overproduction of fibroblast growth factor 23 (FGF23), resulting in hyperphospaturia, hypophosphatemia, and osteomalacia. Surgery is the only definitive treatment, but tumor can locally recur, even after years from primary surgery. Furthermore, some tumors cannot be removed by surgery due to their location. METHODS: We describe the case of a 54-year-old woman affected by recurrent TIO who, after three unsuccessful surgical attempts of tumor removal, was treated with burosumab, an anti-FGF-23 monoclonal antibody. RESULTS: The patient was referred to our Bone Unit after experiencing several fractures in different sites, both traumatic and non-traumatic. At the time of first evaluation, at the age of 46, serum-phosphate (SP) was 1.2 mg/dL (reference range (RR) 2.5-4.5), 24-h urinary phosphate was 842 mg (RR 400-1000), and intact-FGF-23 was 117 pg/mL (RR 25-45). Imaging showed a metabolic pre-sacral lesion that firstly underwent to exploratory laparotomy. Then, patient underwent to surgical excision of tumor. After 18 months of well-being, tumor relapsed and even the subsequent surgery was not able to completely remove it. Since 2015, patient was maintained in phosphorus supplements and 1,25(OH)2vitamin D3, but SP levels never normalized. In September 2019, she was started on burosumab, initially at the dose of 0.3 mg/kg/month, progressively increased to the current 0.8 mg/kg/month, with great improvement of pain, physical performance, and normalization of SP levels. Burosumab was temporary and cautionary discontinued for COVID-19 pneumonia, with a worsening of SP. After restart of burosumab, biochemistry returned to normal. CONCLUSIONS: To our knowledge, this is the first European patient affected by TIO treated with burosumab for more than 2 years. Burosumab is a promising therapy in the medical treatment of TIO refractory or not eligible for definitive surgery, with good efficacy and safety profile.

Unbalanced diet to lower serum cholesterol level is a risk factor for postmenopausal osteoporosis and distal forearm fracture.

The purpose of this study was to assess whether dietary changes aimed at reducing serum cholesterol can increase the risk of osteoporosis (OP) and fracture. The study group consisted of 311 postmenopausal women with high serum cholesterol levels and following a diet low in dairy products (calcium intake estimated at less than 300 mg/day) for 27.3 +/- 29.1 months. This sample was compared with a case-control group of 622 healthy postmenopausal women paired for age and age at menopause and with a calcium intake estimated at more than 1 g/day. Bone mineral density was measured at the lumbar spine by dual-energy X-ray absorptiometry. Prevalence of OP was significantly higher in women with a low dairy calcium intake (42.1% vs 22.3%; p < 0.0001), as was the number of Colles' fractures occurring after menopause (4.5% vs 1.6%; p = 0.008). Multiple logistic regression analyses demonstrated that a diet low in dairy calcium was a risk factor for OP (OR = 2.52, 95% CI 1.84-3.45) and Colles' fracture (OR = 2.72, 95% CI 1.18-6.26). In the low dairy calcium group, diet duration significantly influenced the risk of OP (OR = 1.13, 95% CI 1.01-1.25 for 1 year of diet). No differences in further risk factors for coronary heart disease were found between the groups, but the proportion of women physically active was lower in the women with high serum cholesterol levels. A diet that severely limits calcium intake from dairy products in an attempt to correct raised serum cholesterol levels is a risk factor for postmenopausal OP and Colles' fracture. Dietary intervention methods to lower serum cholesterol in postmenopausal women should maintain an adequate calcium intake by providing calcium from low-fat dairy products or calcium supplements.