Abnormalities in Muscle Density and Muscle Function in Hypophosphatemic Rickets

Veilleux, Louis‐Nicolas; Cheung, Moira; Amor, Mouna Ben; Rauch, Frank

doi:10.1210/jc.2012-1336

Cited by 58 publications

(67 citation statements)

References 29 publications

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“…Children carriers of any of these mutations have soft bones (rickets), growth retardation, poor dental development, and elevated serum FGF23 levels [46]. It has been shown that accumulation of FGF23 is strongly associated with muscle function abnormalities in humans [47, 48].…”

Section: Human and Animal Bone-focused Knock-out “Models” Comprising mentioning

confidence: 99%

Genetics of Bone and Muscle Interactions in Humans

Trajanoska

Rivadeneira

Kiel

et al. 2019

Curr Osteoporos Rep

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Purpose of ReviewTo summarize the evidence from recent studies on the shared genetics between bone and muscle in humans.Recent FindingsGenome-wide association studies (GWAS) have successfully identified a multitude of loci influencing the variability of different bone or muscle parameters, with multiple loci overlapping between the traits. In addition, joint analyses of multiple correlated musculoskeletal traits (i.e., multivariate GWAS) have underscored several genes with possible pleiotropic effects on both bone and muscle including MEF2C and SREBF1. Notably, several of the proposed pleiotropic genes have been validated using human cells or animal models.SummaryIt is clear that the study of pleiotropy may provide novel insights into disease pathophysiology potentially leading to the identification of new treatment strategies that simultaneously prevent or treat both osteoporosis and sarcopenia. However, the role of muscle factors (myokines) that stimulate bone metabolism, as well as osteokines that affect muscles, is in its earliest stage of understanding.

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Section: Human and Animal Bone-focused Knock-out “Models” Comprising mentioning

confidence: 99%

Genetics of Bone and Muscle Interactions in Humans

Trajanoska

Rivadeneira

Kiel

et al. 2019

Curr Osteoporos Rep

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“…Adults with XLH are prone to pseudofractures and fractures due to a combination of osteomalacia and skeletal deformities resulting from rickets in childhood that expose long bones to abnormal biomechanical stress . In addition, many patients have early and accelerated osteoarthritis in weight‐bearing joints, lower limb deformities, acquired joint malalignment, enthesopathy, and muscle function deficits . These musculoskeletal abnormalities are prominent and debilitating features in adults with XLH that cause pain and stiffness, impairing mobility and physical function, and reducing health‐related quality of life …”

Section: Introductionmentioning

confidence: 99%

A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial Evaluating the Efficacy of Burosumab, an Anti-FGF23 Antibody, in Adults With X-Linked Hypophosphatemia: Week 24 Primary Analysis

Insogna

Briot

Imel

et al. 2018

Journal of Bone and Mineral Research

260

269

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In X-linked hypophosphatemia (XLH), inherited loss-of-function mutations in the PHEX gene cause excess circulating levels of fibroblast growth factor 23 (FGF23), leading to lifelong renal phosphate wasting and hypophosphatemia. Adults with XLH present with chronic musculoskeletal pain and stiffness, short stature, lower limb deformities, fractures, and pseudofractures due to osteomalacia, accelerated osteoarthritis, dental abscesses, and enthesopathy. Burosumab, a fully human monoclonal antibody, binds and inhibits FGF23 to correct hypophosphatemia. This report summarizes results from a double-blind, placebo-controlled, phase 3 trial of burosumab in symptomatic adults with XLH. Participants with hypophosphatemia and pain were assigned 1:1 to burosumab 1 mg/kg (n ¼ 68) or placebo (n ¼ 66) subcutaneously every 4 weeks (Q4W) and were comparable at baseline. Across midpoints of dosing intervals, 94.1% of burosumab-treated participants attained mean serum phosphate concentration above the lower limit of normal compared with 7.6% of those receiving placebo (p < 0.001). Burosumab significantly reduced the Western Ontario and the McMaster Universities Osteoarthritis Index (WOMAC) stiffness subscale compared with placebo (least squares [LS] mean AE standard error [SE] difference, -8.1 AE 3.24; p ¼ 0.012). Reductions in WOMAC physical function subscale (-4.9 AE 2.48; p ¼ 0.048) and Brief Pain Inventory worst pain (-0.5 AE 0.28; p ¼ 0.092) did not achieve statistical significance after Hochberg multiplicity adjustment. At week 24, 43.1% (burosumab) and 7.7% (placebo) of baseline active fractures were fully healed; the odds of healed fracture in the burosumab group was 16.8-fold greater than that in the placebo group (p < 0.001). Biochemical markers of bone formation and resorption increased significantly from baseline with burosumab treatment compared 1383with placebo. The safety profile of burosumab was similar to placebo. There were no treatment-related serious adverse events or meaningful changes from baseline in serum or urine calcium, intact parathyroid hormone, or nephrocalcinosis. These data support the conclusion that burosumab is a novel therapeutic addressing an important medical need in adults with XLH.

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“…As 27 muscle force and bone mass are usually closely related, we hypothesized that muscle weakness in OI type I 28 could contribute to increase bone mass deficit in the lower extremities. 29 Objective: To assess the muscle-bone relationship in the lower extremities of children and adolescents with OI 30 type I. 31 Setting: The study was carried out in the outpatients department of a pediatric orthopedic hospital.…”

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confidence: 99%