Dietary recommendations in the prevention and treatment of osteoporosis.

INTRODUCTION: This article presents the initial recommendations of the French Rheumatology Society (Société Française de Rhumatologie - SFR) and the Osteoporosis Research and Information Group (Groupe de Recherche et d'Informations sur les Ostéoporoses - GRIO) on the role of diet in the prevention and treatment of osteoporosis. METHODS: The recommendations were produced by a working group composed of rheumatologists, physician nutrition specialists and a geriatrician. Fifteen (15) questions pertaining to "daily practices" were preselected by the working group. For the literature review, the working group focussed mainly on the effects of diet on bone mineral density (BMD) and fractures, and primarily on meta-analyses of longitudinal studies and dietary intervention studies. RESULTS: A Mediterranean-type diet and the daily consumption of 2 to 3 dairy products are recommended. Together, these provide the calcium and "high quality" protein required to maintain a normal calcium-phosphorus balance and bone metabolism, and are associated with lower fracture risk. Conversely, unbalanced Western diets, vegan diets, weight-loss diets in non-overweight individuals, alcohol consumption and daily consumption of sodas are advised against. In terms of the beneficial effects on bone mineral density and fracture risk, current scientific data are either insufficient or too divergent to recommend increasing or restricting the consumption of tea or coffee, vitamins other than vitamin D, vitamin D-enriched or phytoestrogen-rich foods, calcium-enriched plant-based beverages, oral nutritional supplements, or dietary sources of prebiotics and probiotics. CONCLUSIONS: These are the first set of recommendations addressing the role of diet in the prevention and treatment of osteoporosis. More research is necessary to direct and support guidelines.

Bisphosphonates for the treatment of fibrous dysplasia of bone.

INTRODUCTION: Fibrous dysplasia of bone (FD) is a rare congenital bone disease, due to a somatic mutation of GNAS. This mutation results in a defect of osteoblast differentiation and mineralization and also an increase in bone resorption by large active osteoclasts. Bone pain is present in half of patients and is the main determinant of quality of life of patients with FD. Bisphosphonates are known to reduce bone pain and reduce the risk of fracture in patients with bone metastases or Paget's disease. Bisphosphonates may have similar effects in FD. In this article, we have reviewed the therapeutic potential of bisphosphonates to reduce bone pain due to FD, improve bone strength and reduce the occurrence of fracture. MATERIAL AND METHODS: We have reviewed 234 articles examining the effect of bisphosphonates on FD/McCune Albright Syndrome with no date limit, in PubMed and selected the articles with highest quality of methodology. RESULTS: Pamidronate therapy significantly decreased bone pain and bone resorption (urinary NTX, urinary and serum CTX). Pamidronate may improve radiological lesions of FD patients (filling of osteolytic lesion and/or cortical thickening). This data with intravenous pamidronate, however, has been obtained from observational studies and no randomized controlled trial is available. Randomized placebo-controlled trials of oral bisphosphonates (alendronate or risedronate) have failed to demonstrate a significant decrease in bone pain over placebo. Several studies including one randomized controlled trial have shown an increase in bone mineral density (BMD) at FD sites with oral and intravenous bisphosphonate treatment. No effect on occurrence of fracture has been reported. CONCLUSION: In conclusion, intravenous bisphosphonates may be proposed to treat persistent, moderate to severe bone pain of FD, e.g., according to the guidelines from the FD/MAS International Consortium. Oral bisphosphonates should not be used in this indication.

A Signature of Circulating miRNAs Associated With Fibrous Dysplasia of Bone: the mirDys Study.

Fibrous dysplasia (FD) is a rare bone disease caused by activating mutations of GNAS encoding the Gsα protein, enhancing cyclic adenosine monophosphate (cAMP) production by overstimulation of adenylyl cyclase and impairing osteoblastic differentiation. The clinical presentation ranges from asymptomatic to polyostotic forms with severe disability, explained by the mosaic distribution of the GNAS mutation. Physicians have to deal with the gap of knowledge in FD pathogenesis, the absence of prognostic markers and the lack of specific treatment. The identification of specific biomarkers for FD is an important step to improve the clinical and therapeutic approaches. An epigenetic regulation driven by microRNAs (miRNAs), known as promising biomarkers in bone disease, could be involved in FD. We have sought circulating miRNAs that are differentially expressed in FD patients compared to controls and would reflect dysregulations of osteogenesis-related genes and bone disorder. The global miRNA profiling was performed using Next Generation Sequencing in patient serum collected from a discovery cohort of 20 patients (10 polyostotic and 10 monostotic) and 10 controls. From these, we selected 19 miRNAs for a miRNA validation phase from serum of 82 patients and 82 controls, using real-time qPCR. Discovery screening identified 111 miRNAs differentially expressed in patient serum, after adjusting for the false discovery rate (FDR). Among the 82 patients, 55% were polyostotic, and 73% were women with a mean age of 42 years. Six miRNAs (miR-25-3p, miR-93-5p, miR-182-5p, miR-324-5p, miR-363-3p, and miR-451a) were significantly overexpressed in serum, with FDR <0.05. The expression level of these six miRNAs was not associated with the FD severity. In conclusion, we identified a signature of circulating miRNAs associated with FD. These miRNAs are potential negative regulators of gene expression in bone cell progenitors, suggesting their activity in FD by interfering with osteoblastic and osteoclastic differentiation to impair bone mineralization and remodeling processes. © 2020 American Society for Bone and Mineral Research.