Compromised Volumetric Bone Density and Microarchitecture in Men With Congenital Hypogonadotropic Hypogonadism.

Context: Men with congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS) have both low circulating testosterone and estradiol levels. Whether bone structure is affected remains unknown.

Objective: To characterize bone geometry, volumetric density and microarchitecture in CHH/KS.

Sclerosing bone dysplasias with hallmarks of dysosteosclerosis in four patients carrying mutations in SLC29A3 and TCIRG1.

The osteopetroses and related sclerosing bone dysplasias can have a broad range of manifestations. Especially in the milder forms, sandwich vertebrae are an easily recognizable and reliable radiological hallmark. We report on four patients from three families presenting with sandwich vertebrae and platyspondyly.

Variations of SOST mRNA expression in human bone are associated with DNA polymorphism and DNA methylation in the SOST gene.

SOST encodes sclerostin, an inhibitor of bone formation that antagonizes canonical Wnt signaling. Variations of SOST expression have an impact on bone mineral density (BMD) and bone strength. We hypothesized that genetic and epigenetic DNA modifications have an impact on SOST gene expression.

Disrupted trabecular bone micro-architecture in middle-aged male HIV-infected treated patients.

Objectives: HIV-infected individuals are at increased risk of incident fractures. Evaluation of trabecular bone micro-architecture is an important tool to assess bone strength, but its use has not yet been reported in middle-aged HIV-infected male individuals. The aim of the study was to compare bone micro-architecture between HIV-infected and HIV-uninfected men.

Serotonin Is Involved in Autoimmune Arthritis through Th17 Immunity and Bone Resorption.

Rheumatoid arthritis is a chronic disease that results in a disabling and painful condition as it progresses to destruction of the articular cartilage and ankylosis of the joints. Although the cause of the disease is still unknown, evidence argues that autoimmunity plays an important part. There are increasing but contradictory views regarding serotonin being associated with activation of immunoinflammatory pathways and the onset of autoimmune reactions.

Osteopetrosis and its relevance for the discovery of new functions associated with the skeleton.

Osteopetrosis is a rare genetic disorder characterized by an increase of bone mass due to defective osteoclast function. Patients typically displayed spontaneous fractures, anemia, and in the most severe forms hepatosplenomegaly and compression of cranial facial nerves leading to deafness and blindness. Osteopetrosis comprises a heterogeneous group of diseases as several forms are known with different models of inheritance and severity from asymptomatic to lethal.

When, how, and why a bone biopsy should be performed in patients with chronic kidney disease.

In chronic kidney disease the excessive production of parathyroid hormone increases the bone resorption rate and leads to histologic bone signs of secondary hyperparathyroidism. However, in other situations, the initial increase in parathyroid hormone and bone remodeling may be slowed down excessively by a multitude of factors including age, ethnic origin, sex, and treatments such as vitamin D, calcium salts, calcimimetics, steroids, and so forth, leading to low bone turnover or adynamic bone disease. Both high and low bone turnover diseases actually are observed equally in chronic kidney disease patients treated by dialysis, and all types of renal osteodystrophy are associated with an increased risk of skeletal fractures, reduced quality of life, and poor clinical outcomes.

Ankle-brachial index and bone turnover in patients on dialysis.

An association between atherosclerosis and osteoporosis has been reported in several studies. This association could result from local intraosseous atherosclerosis and ischemia, which is shown by limb osteoporosis in patients with peripheral artery disease (PAD), but also could result from bidirectional communication between the skeleton and blood vessels. Systemic bone disorders and PAD are frequent in ESRD.

Bone status and fractures in 85 adults with Wilson's disease.

Unlabelled: Wilson's disease is characterized by copper deposition, especially in the liver and central nervous system. We assessed the prevalent fractures and bone mineral density (BMD) and related risk factors in 85 patients. BMD was normal, but patients with severe neurological involvement, low BMI, and/or amenorrhea are at risk for fractures.

Cortical measurements of the tibia from high resolution peripheral quantitative computed tomography images: a comparison with synchrotron radiation micro-computed tomography.

High resolution-peripheral quantitative computed tomography (HR-pQCT) measurements are carried out in clinical research protocols to analyze cortical bone. Micro-computed tomography (micro-CT) is a standard tool for ex vivo examination of bone in 3D. The aim of this work was to evaluate cortical measurements derived from HR-pQCT images compared to those from synchrotron radiation (SR) micro-CT in a distal position (4.

ClC-7 expression levels critically regulate bone turnover, but not gastric acid secretion.

Mutations in the 2Cl(-)/1H(+)-exchanger ClC-7 impair osteoclast function and cause different types of osteoclast-rich osteopetrosis. However, it is unknown to what extent ClC-7 function has to be reduced to become rate-limiting for bone resorption. In osteoclasts from osteopetrosis patients expression of the mutated ClC-7 protein did not correlate with disease severity and resorption impairment.

Serotonin 2B receptor (5-HT2B R) signals through prostacyclin and PPAR-ß/δ in osteoblasts.

Osteoporosis is due to an imbalance between decreased bone formation by osteoblasts and increased resorption by osteoclasts. Deciphering factors controlling bone formation is therefore of utmost importance for the understanding and the treatment of osteoporosis. Our previous in vivo results showed that bone formation is reduced in the absence of the serotonin receptor 5-HT2B, causing impaired osteoblast proliferation, recruitment, and matrix mineralization.

Camurati-Engelmann disease with obesity in a newly identified family carrying a missense p.Arg156Cys mutation in the TGFB1 gene.

We report on a family affected by Camurati-Engelmann disease, characterized by radiological signs limited to the tibia, and associated with overweight or obesity, which is not a known feature of this disorder. The affected patients were heterozygous for a c.466C > T mutation (which predicts p.

Alteration of proteoglycan sulfation affects bone growth and remodeling.

Diastrophic dysplasia (DTD) is a chondrodysplasia caused by mutations in the SLC26A2 gene, leading to reduced intracellular sulfate pool in chondrocytes, osteoblasts and fibroblasts. Hence, proteoglycans are undersulfated in the cartilage and bone of DTD patients. To characterize the bone phenotype of this skeletal dysplasia we used the Slc26a2 knock-in mouse (dtd mouse), that was previously validated as an animal model of DTD in humans.

A case-control study of fractures in men with idiopathic osteoporosis: fractures are associated with older age and low cortical bone density.

Objectives: To determine biochemical, radiological and micro-architectural bone factors related to fragility fractures in idiopathic male osteoporosis (IMO) patients. IMO is a rare disorder characterized by low areal bone mineral density (aBMD) (Z-score<-2) occurring in men after excluding secondary causes of low BMD.

Methods: We conducted a case-control study in 31 patients with fragility fracture (IMO F+) that had occurred after the age of 40 years and 37 without fracture (IMO F-).

Osteoporosis in young adults: pathophysiology, diagnosis, and management.

Postmenopausal osteoporosis is mainly caused by increased bone remodeling resulting from estrogen deficiency. Indications for treatment are based on low areal bone mineral density (aBMD, T-score  ≤ -2.5), typical fragility fractures (spine or hip), and more recently, an elevated 10-year fracture probability (by FRAX®).

Targeting bone alleviates osteoarthritis in osteopenic mice and modulates cartilage catabolism.

Objective: Subchondral bone modifications occur early in the development of osteoarthritis (OA). The level of bone resorption might impact cartilage remodeling. We therefore assessed the in vivo and in vitro effects of targeting bone resorption in OA and cartilage metabolism.

Effect of oral monthly ibandronate on bone microarchitecture in women with osteopenia-a randomized placebo-controlled trial.

Unlabelled: We have examined the effect of oral monthly ibandronate on distal radius and tibia microarchitecture with high-resolution peripheral quantitative tomography compared with placebo, in women with osteopenia, and found that ibandronate did not significantly affect trabecular bone but improved cortical density and thickness at the tibia.

Methods: We have examined the effect of ibandronate on bone microarchitecture with peripheral high-resolution quantitative computed tomography (HR-pQCT) in a randomized placebo-controlled trial among 148 women with osteopenia. Patients received either oral 150 mg monthly ibandronate or placebo over 24 months.

An activating Fgfr3 mutation affects trabecular bone formation via a paracrine mechanism during growth.

The fibroblast growth factor receptor 3 (FGFR3) plays a critical role in the regulation of endochondral ossification. Fgfr3 gain-of-function mutations cause achondroplasia, the most common form of dwarfism, and a spectrum of chondrodysplasias. Despite a significant number of studies on the role of FGFR3 in cartilage, to date, none has investigated the influence of Fgfr3-mediated effects of the growth plate on bone formation.

Decreased osteoclastogenesis in serotonin-deficient mice.

Peripheral serotonin, synthesized by tryptophan hydroxylase-1 (TPH(1)), has been shown to play a key role in several physiological functions. Recently, controversy has emerged about whether peripheral serotonin has any effect on bone density and remodeling.We therefore decided to investigate in detail bone remodeling in growing and mature TPH(1) knockout mice (TPH(1)(-/-)).

Serotonin: good or bad for bone.

Besides its action as a neurotransmitter, serotonin has multiple physiological functions in several peripheral organs. Recently, Yadav et al. suggested that peripheral serotonin produced in the gut was a major negative regulator of osteoblast proliferation.

Assessment of dynamic humeral centering in shoulder pain with impingement syndrome: a randomised clinical trial.

Objectives: Treatment for degenerative rotator cuff disease of the shoulder includes physiotherapy. Dynamic humeral centering (DHC) aims at preventing subacromial impingement, which contributes to the disease. The goal of this study was to assess the effectiveness of DHC.