Denosumab use in bone fibrous dysplasia refractory to bisphosphonate: A retrospective multicentric study.

INTRODUCTION: Increased RANKL expression is observed in the bone tissue of fibrous dysplasia of bone/McCune-Albright syndrome (FD/MAS). In one animal model of FD/MAS, the inhibition of RANKL reduced tumor volume. A beneficial effect of denosumab on pain in patients refractory to bisphosphonates has been reported, but without systematic quantification of pain improvement. This work describes the clinical experience of our group on the efficacy on pain of denosumab treatment, along with safety, in FD/MAS patients refractory to bisphosphonates. MATERIALS AND METHODS: We have conducted a retrospective multicenter study in 6 academic rheumatology centers in France. We have collected patients and FD/MAS characteristics, duration of prior exposure to bisphosphonates, denosumab treatment modalities (dosage - administration regimen - number of courses); evolution of pain evaluated by Visual Analogic Scale (VAS). RESULTS: 13 patients were included (10 women and 3 men) 45 years on average, 5 MAS, 4 monostotic and 4 polyostotic forms. The average duration post-diagnosis of FD/MAS was 25 years and the mean duration of prior exposure to bisphosphonates was 4.7 years. Pain could be analyzed in 7 patients, showing a significant improvement from a mean VAS of 7.8 to 2.9 (-4.9 points, p = 0.003). In one patient with fronto-orbital FD/MAS, a 30 % decrease in lesional volume, assessed by MRI, was observed within 6 months of treatment, that was sustained over the following 12 months. Treatment regimens were heterogeneous. No hypercalcemia was observed after treatment cessation and the clinical tolerance was good. DISCUSSION: This study suggests that denosumab reduces pain in patients with DF/MAS refractory to bisphosphonates, and quantifies this improvement for the first time in a multicenter study. In our cohort, no patients who discontinued denosumab developed hypercalcemia and clinical tolerance was overall good. This study also provides encouraging data regarding lesion volume control. Further controlled studies are required to determine the place and modalities of the denosumab treatment of FD/MAS. CONCLUSION: Denosumab significantly decreased pain in FD/MAS refractory to bisphosphonate. This study paves the way for a randomized clinical trial to validate and standardize the prescription of denosumab in FD/MAS.

Long-Term Effects of Roux-en-Y Gastric Bypass and Sleeve Gastrectomy on Bone Mineral Density: a 4-Year Longitudinal Study.

INTRODUCTION: Bone mineral density (BMD) declines in the initial years after bariatric surgery, but long-term skeletal effects are unclear and comparisons between sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are rare. DESIGN AND METHODS: An observational longitudinal study of obese patients undergoing SG or RYGB was performed. Whole-body (WB) BMD, along with BMD of the total hip (TH), femoral neck (FN), and lumbar spine (LS), was measured by dual-energy X-ray absorptiometry (DXA) before surgery and yearly thereafter for 4 years. Calciotropic hormones were also measured. RESULTS: Forty-seven patients undergoing RYGB surgery and 28 patients undergoing SG were included. Four years after RYGB, BMD declined by 2.8 ± 5.8% in LS, 8.6 ± 5% in FN, 10.9 ± 6.3% in TH, and 4.2 ± 6.2% in WB, relative to baseline. For SG, BMD declined by 8.1 ± 5.5% in FN, 7.7 ± 6% in TH, 2.0 ± 7.2% in LS, and 2.5 ± 6.4% in WB after 4 years, relative to baseline. Vitamin D levels increased with supplementation in both groups. Whereas parathyroid hormone levels increased slightly in the RYGB group, they decreased modestly in the SG group (P < 0.05 in both groups). CONCLUSIONS: Bone loss after 4 years was comparable between the two procedures, although RYGB was associated with a slightly greater decrease at the TH than SG. Bone health should therefore be monitored after both RYGB and SG.

Vertebral fractures cascade: potential causes and risk factors.

We performed a study to identify potential causes and risk factors of vertebral fracture cascade. Vertebral fracture cascade is a severe clinical event in patients with bone fragility. Only half of patients have an identified cause of secondary osteoporosis. INTRODUCTION: Vertebral fracture (VF) is the most common osteoporotic fracture, and a strong risk factor of subsequent VFs leading to VF cascade (VFC). We prompted a study to identify potential causes and risk factors of VFC. METHODS: VFC observations were collected retrospectively between January 2016 and April 2017. VFC was defined as an occurrence of at least three VFs within 1 year. RESULTS: We included in 10 centers a total of 113 patients with VFC (79.6% of women, median age 73, median number of VFs in the cascade, 5). We observed 40.5% and 30.9% of patients with previous major fractures and a previous VF, respectively, and 68.6% with densitometric osteoporosis; 18.9% of patients were currently receiving oral glucocorticoids and 37.1% in the past. VFC was attributed by the physician to postmenopausal osteoporosis in 54% of patients. A secondary osteoporosis associated with the VFC was diagnosed in 52 patients: glucocorticoid-induced osteoporosis (25.7%), non-malignant hemopathies (6.2%), alcoholism (4.4%), use of aromatase inhibitors (3.6%), primary hyperparathyroidism (2.7%), hypercorticism (2.7%), anorexia nervosa (2.7%), and pregnancy and lactation-associated osteoporosis (1.8%). A total of 11.8% of cases were reported following a vertebroplasty procedure. A total of 31.5% patients previously received an anti-osteoporotic treatment. In six patients, VFC occurred early after discontinuation of an anti-osteoporotic treatment, in the year after the last dose effect was depleted: five after denosumab and one after odanacatib. CONCLUSION: The results of this retrospective study showed that only half of VFC occurred in patients with a secondary cause of osteoporosis. Prospective studies are needed to further explore the determinants of this severe complication of osteoporosis.