Deficits In Bone Mass Research Articles

Updated reference values for BMD and lean mass measured by DXA in Thai children.

This study established normative references for total body less head (TBLH) BMD, lumbar spine (L1-L4) BMD, and both total and appendicular lean mass (LM) in Thai children and adolescents (aged 5-18years) using DXA. This work expands upon 2014 normative data for Thai children, which included L2-L4 BMD, total body BMD (head included), and total LM. We reanalyzed total body and lumbar spine DXA scans (Lunar Prodigy Pro, GE Healthcare; enCORE version 7.53) from 174 boys and 193 girls, using upgraded software (enCORE version 17SP2) for TBLH BMD, L1-L4 BMD, and LM analysis. The "enhanced" mode was applied for TBLH BMD and LM. Adjustments for total and appendicular LM were made relative to squared height (m2) to account for body size variability. Normative data stratified by sex and Tanner stage were generated for TBLH BMD, L1-L4 BMD, and LM indices. Weight and Tanner stage significantly determined BMD and LM. Adolescent girls exhibited higher LSBMD values due to earlier pubertal onset. Boys showed higher LM indices with more rapid gains during growth spurts. This study provides updated normative reference values for BMD (TBLH and L1-L4) and LM (total and appendicular) in Thai children and adolescents, measured via DXA. These references will enhance the assessment of low bone mass and LM deficits in Thai pediatric populations, particularly in those with chronic illnesses.

Improving compliance to DEXA in IBD population according to BSG guidelines in Morriston Hospital, Swansea

Individuals with inflammatory bowel disease (IBD) have an increased risk of osteoporosis compared with the general population.[1,2][1] Bone disease is attributed to vitamin D deficiency, steroid use, and/or systemic inflammation[3][2] and deficits in bone mass can persist despite absence of symptoms

Mice with Targeted Knockout of Tetraspanin 3 Exhibit Reduced Trabecular Bone Mass Caused by Decreased Osteoblast Functions.

Tetraspanin3 (TSPAN3) was identified as a binding partner of claudin11 (CLDN11) in osteoblasts and other cell types. Mice with targeted disruption of Cldn11 exhibited trabecular bone mass deficit caused by reduced bone formation and osteoblast function. To determine if the disruption of CLDN11 interacting protein gene Tspan3 results in a similar skeletal phenotype as that of Cldn11 knockout (KO) mice, we generated homozygous Tspan3 KO and heterozygous control mice and characterized their skeletal phenotypes at 13 weeks of age. Micro-CT measurements of the secondary spongiosa of the distal femur revealed 17% and 29% reduction in trabecular bone volume adjusted for tissue volume (BV/TV) in the male and female mice, respectively. Similarly, trabecular BV/TV of the proximal tibia was reduced by 19% and 20% in the male and female mice, respectively. The reduced trabecular bone mass was caused primarily by reduced trabecular thickness and number, and increased trabecular spacing. Consistent with the reduced bone formation as confirmed by histomorphometry analyses, serum alkaline phosphatase was reduced by 11% in the KO mice as compared with controls. Our findings indicate that TSPAN3 is an important positive regulator of osteoblast function and trabecular bone mass, and the interaction of TSPAN3 with CLDN11 could contribute in part to the bone forming effects of Cldn11 in mice.

Injuries of the thoracic and lumbar spine due to juvenile osteoporosis

Complex examination of 123 children with back pain and wedge-shaped vertebra body deformity (according to X-ray data) showed that those changes were the manifestation of juvenile osteoporosis in 10,5%) of cases. Diagnosis of juvenile osteoporosis was confirmed by the decrease of bone mass by 10%) and over versus the norm. It was detected using DEXA. Conformity of that bone loss to osteoporosis was proved by comparative histomorphometry of bioptate from the upper flaring portion of the ileum in patients with BMD loss. Comparison of histomorphometry data and activity of the bone marrow stromal cell clonning showed that BMD loss was connected with the decrease of bone formation; the later was stipulated by genetic defect of osteoblasts cellprecursors. Those changes preceded to bone mass loss that could be detected by invasive or noninvasive methods. The possibility of pharmacological correction of bone mass deficit in children was shown.

Development of tibia & fibula bone deficits in children with neurofibromatosis type I - A longitudinal case-control comparison.

Neurofibromatosis type 1 (NF1) is associated with lower bone mass and increased risk of fracture. Children with NF1 display faltering growth from mid-childhood. However, to date tibia bone development in children with NF1 across childhood and the role of body size have not been explored. Therefore, we recruited 24 children with NF1 (12 girls, mean age 8.2±1.1y) and 104 children without NF1 (52 girls, mean age 11±1.7y). Tibia and fibula bone characteristics were assessed at 4% and 38% distal-proximal tibia length in all children at baseline using peripheral quantitative computed tomography (pQCT). Longitudinal scans were obtained in 21 children with NF1 (12 girls) over 3.4±0.3y and 71 children without NF1 (34 girls) over 1.1±0.1y, such that at follow-up mean age of both groups (NF1 10.9±1.3y, controls 11.4±1.4y) were similar. Effects of group (NF1/control) on bone outcomes as well as group-by-age interactions, indicating differences in rate of change in bone outcome bone outcomes were assessed via linear mixed effects models with adjustment for sex, age, pubertal status and in additional models with adjustment for height and weight Z-scores. Group (NF1/control)-by-age interactions indicated a slower rate of tibia and fibula bone mass accrual in children with NF1 at all measured sites. These associations were attenuated by 25-50% by adjustment for height and weight Z-scores. At the 4% site, deficits in bone mass at older ages were related to slower trabecular BMD accrual. At the 38% site, group-by-age interactions suggested that bone mass deficits resulted from poorer accrual of cortical CSA and to a lesser extent cortical BMD. Lower limb bone mass deficits evident in children with NF1 appear to be progressive and emerge in mid-childhood. In part, they are related to development of a similar pattern of deficits in longitudinal growth and body weight in NF1. Interventions promoting muscle development or physical activity may be partially effective in attenuating bone mass accrual deficits in this population.

Case Report: Low Bone and Normal Lean Mass in Adolescents With Complete Androgen Insensitivity Syndrome

IntroductionOsteopenia and osteoporosis have been reported in adults with Complete Androgen Insensitivity Syndrome (CAIS). Little is known about changes in bone mineral density (BMD) in adolescents with CAIS and whether it is affected by early gonadectomy. Body composition data have not been reported.MethodsSingle-center, retrospective study of CAIS adolescents who underwent dual-energy x-ray absorptiometry (DXA) (Hologic, Horizon A). Body composition is presented as lean and fat mass indices (LMI, FMI). Z-scores for lumbar spine areal BMD (LBMD), total body less head (TBLH), bone mineral content (BMC), LMI, and FMI were calculated using female normative data. Results are expressed as median and min, max.ResultsSix females with genetically confirmed CAIS were identified—one with intact gonads and five with history of gonadectomy at 2–11 months. In the subject with intact gonads, LBMD-Z and TBLH BMC-Z were −1.56 and −1.26, respectively, at age 16 years. Among those with gonadectomy, LBMD-Z was −1.8 (−3.59 to 0.49) at age 15.6 years (12–16.8) and decreased in all three subjects who had longitudinal follow-up despite hormone replacement therapy (HRT). Adherence to HRT was intermittent. LMI-Z and FMI-Z were 0.1 (−1.39 to 0.7) and 1.0 (0.22 to 1.49), respectively.ConclusionsThese limited data indicate that adolescents with CAIS have bone mass deficit. Further studies are needed to understand the extent of BMD abnormalities and the effect of gonadectomy, especially early in childhood, and to establish the optimal HRT regimen for bone accrual. Data on lean mass are reassuring.

Bone mineral density and oxidative stress in adolescent girls with anorexia nervosa

Oxidative stress appears to be involved in the pathogenesis of osteoporosis-a serious complication of anorexia nervosa (AN). We evaluated the oxidative status in adolescent girls with AN and its potential relationship with bone mineral density (BMD). Girls with AN (n = 43) and age-matched healthy controls (n = 20) underwent anthropometric and BMD examination. Markers of bone turnover, oxidative stress, and antioxidant status were measured. Participants with AN and controls did not differ in BMD at the lumbar spine (p = 0.17) and total body less head BMD (p = 0.08). BMD at the total hip was lower (p < 0.001) in the AN group compared with the controls. Levels of antioxidant status markers-ferric reduction antioxidant power, total antioxidant capacity, and reduced and oxidized glutathione ratio (all p < 0.001)-were significantly lower, whereas those of advanced oxidation protein products (AOPP), fructosamines, and advanced glycation end products (AGEs) (all p < 0.001) were higher in AN patients than in healthy controls. BMD and bone turnover markers were positively correlated with antioxidant status markers, while they were negatively correlated with AOPP, fructosamines, and AGEs levels. Conclusion: This is the first study to assess a potential association between oxidative status and BMD in adolescents with AN. We demonstrated that in young girls, the imbalance of oxidative status and reduced BMD are concurrently manifested at the time of the diagnosis of AN. Disturbance of oxidative status could play a pathogenetic role in AN-associated decreased BMD. What is Known: • Osteoporosis is a serious complication of AN, and in affected adolescents may result in a permanent deficit in bone mass. • Oxidative and carbonyl stress may be involved in the development of bone loss. What is New: • Adolescents girls with AN have impaired antioxidant defense and increased oxidative damage to biomolecules. • Disturbance of oxidative status could affect bone loss and could contribute to decreased BMD in adolescent females with AN.

Cortical Bone Mass is Low in Boys with Klinefelter Syndrome and Improves with Oxandrolone.

ContextKlinefelter syndrome (KS) is the most common sex aneuploidy in men. Affected males have hypogonadism, and, as a result, face an increased risk for osteoporosis and fractures. Androgen therapy is standard in adolescents and adults with KS but has not been used earlier in childhood.ObjectiveTo determine the effects of androgen treatment on bone mass in children with KS.MethodsRandomized, double-blind, placebo-controlled clinical trial of oxandrolone (OX; 0.06 mg/kg daily; n = 38) versus placebo (PL; n = 40) for 2 years in boys with KS (ages 4-12 years). Changes in bone mass were examined by digital x-ray radiogrammetry, which determines the Bone Health Index (BHI) and standard deviation score (SDS).ResultsBHI SDS was similar between groups at baseline (–0.46 ± 1.1 vs –0.34 ± 1.0 OX vs PL, P > .05) and higher in the OX group at 2 years (–0.1 ± 1.3 vs –0.53 ± 0.9, OX vs PL, P < .01). At baseline, BHI SDS values of all subjects were not normally distributed with 25.7% of subjects plotted below –1 SDS (P < .001), suggesting a deficit in bone mass. In total, 13.5% of subjects had sustained a fracture and their BHI SDS was lower than those with no fractures (–1.6 ± 1.3 vs –0.3 ± 1.0, P = .004).ConclusionBone mass using BHI SDS is reduced in some children with KS and improves with OX. Since these individuals are at risk for osteoporosis, age-appropriate androgen replacement and future studies on bone health in children with KS should be further explored.

Abaloparatide treatment increases bone formation, bone density and bone strength without increasing bone resorption in a rat model of hindlimb unloading.

Disuse osteoporosis can result from prolonged bed rest, paralysis, casts, braces, fractures and other conditions. Abaloparatide (ABL) is a PTHrP analog that increases bone density and strength by stimulating osteogenesis with limited effects on bone resorption. We examined skeletal responses to abaloparatide in young adult male rats with normal weight-bearing and with hindlimb unloading via a pelvic harness. Rats were allocated to four groups (10-12 per group): normal weight-bearing plus vehicle treatment (CON-VEH), normal weight-bearing plus ABL treatment (CON-ABL), hindlimb-unloading plus vehicle (HLU-VEH), or hindlimb-unloading plus ABL (HLU-ABL). Rats received ABL (25μg/kg/day, s.c.) or vehicle throughout the 28-day unloading period and were then sacrificed, at which time HLU-VEH rats exhibited reduced bone formation and significant deficits in tibial, femoral, and vertebral bone mass compared with CON-VEH. ABL treatment increased serum osteocalcin in CON and HLU animals while having no effect on the osteoclast marker TRACP-5b. Longitudinal peripheral quantitative computed tomography (pQCT) indicated that ABL increased trabecular and cortical bone mass in the tibia. ABL was also associated with improved trabecular and cortical bone mass and architectural parameters at the femur, tibia, and vertebrae by μCT. Tibial histomorphometry indicated increased trabecular and endocortical bone formation with HLU-ABL versus HLU-VEH and with CON-ABL versus CON-VEH, and ABL was also associated with lower trabecular and endocortical osteoclast surfaces. Vertebral finite element analysis indicated higher ultimate load and stiffness for CON-ABL versus CON-VEH and for HLU-ABL versus HLU-VEH. In summary, ABL was associated with improved trabecular and cortical bone density and architecture in normal weight-bearing and hindlimb-unloaded rats, with higher bone formation and no difference in bone resorption. ABL was also associated with improved bone biomechanical parameters. These results provide rationale for investigating the ability of abaloparatide to prevent or treat disuse osteoporosis in humans.

Linking skeletal muscle aging with osteoporosis by lamin A/C deficiency.

The nuclear lamina protein lamin A/C is a key component of the nuclear envelope. Mutations in the lamin A/C gene (LMNA) are identified in patients with various types of laminopathy-containing diseases, which have features of accelerated aging and osteoporosis. However, the underlying mechanisms for laminopathy-associated osteoporosis remain largely unclear. Here, we provide evidence that loss of lamin A/C in skeletal muscles, but not osteoblast (OB)-lineage cells, results in not only muscle aging-like deficit but also trabecular bone loss, a feature of osteoporosis. The latter is due in large part to elevated bone resorption. Further cellular studies show an increase of osteoclast (OC) differentiation in cocultures of bone marrow macrophages/monocytes (BMMs) and OBs after treatment with the conditioned medium (CM) from lamin A/C-deficient muscle cells. Antibody array screening analysis of the CM proteins identifies interleukin (IL)-6, whose expression is markedly increased in lamin A/C-deficient muscles. Inhibition of IL-6 by its blocking antibody in BMM-OB cocultures diminishes the increase of osteoclastogenesis. Knockout (KO) of IL-6 in muscle lamin A/C-KO mice diminishes the deficits in trabecular bone mass but not muscle. Further mechanistic studies reveal an elevation of cellular senescence marked by senescence-associated beta-galactosidase (SA-β-gal), p16Ink4a, and p53 in lamin A/C-deficient muscles and C2C12 muscle cells, and the p16Ink4a may induce senescence-associated secretory phenotype (SASP) and IL-6 expression. Taken together, these results suggest a critical role for skeletal muscle lamin A/C to prevent cellular senescence, IL-6 expression, hyperosteoclastogenesis, and trabecular bone loss, uncovering a pathological mechanism underlying the link between muscle aging/senescence and osteoporosis.

Bone densities and bone geometry in children and adolescents with arthrogryposis.

To describe bone densitometry results using lumbar spine dual-energy X-ray absorptiometry and forearm peripheral quantitative computed tomography (pQCT) in children with arthrogryposis multiplex congenita (AMC). Prospective study. Lumbar spine areal bone mineral density (BMD) was measured in 58 participants (mean age 6.8years, range 1month to 19.7years; 26 males). The diagnostic subgroup was Amyoplasia in 27 participants, distal arthrogryposis (unclassified, n=13; type 2A, n=1; type 2B, n=2; type 8, n=2) in 18 patients, an unclassified form of arthrogryposis in 6 patients, and a syndromic form of arthrogryposis in 7 patients. The mean lumbar spine areal BMD was -0.4 (SD: 1.5) which was significantly below 0 (p<0.05, one-sample t-test). The mean lumbar spine bone mineral apparent density z-score (+0.4 [SD: 1.4]), a measure that is largely independent of bone size, was not significantly different from 0 (P>0.05). A subset of 22 patients aged 6years or older (mean age 10.9years, 11 males) had forearm pQCT analysis. Mean z-scores for trabecular and cortical volumetric BMD at the radius were similar to healthy controls. Radius periosteal bone circumference and bone mineral content were appropriate for height. These densitometric results did not differ between patients with Amyoplasia or individuals with other diagnoses. Low areal BMD in children and adolescents with AMC reflects their smaller bone size rather than a specific bone mass deficit. These data do not suggest that children and adolescents with AMC in general require regular monitoring by bone densitometry unless there are specific clinical concerns.

Arachidonic acid status negatively associates with forearm bone outcomes and glucose homeostasis in children with an overweight condition or obesity.

Long-chain polyunsaturated fatty acids are implicated in musculoskeletal health in adults. This study examined whether fatty acid status relates to bone health outcomes in children with overweight condition or obesity (body mass index z score, 3.1 ± 0.1; age, 9.0 ± 0.2 years; n = 108). Nondominant forearm bone density (distal one-third), geometry (4% site), and soft tissue composition (66%) were assessed using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Red blood cell (RBC) fatty acid profile and indices of glucose homeostasis were measured. Differences in outcomes among RBC arachidonic acid (AA, C20:4n-6) tertiles were tested using mixed-model ANOVA. Ultra-, mid-, and total-distal forearm bone mineral content, adjusted for sex, age, percentage body fat, race, and forearm length, were 10% to 13% greater in children in the first AA tertile relative to the third. Children in the second tertile had the highest bone cross-sectional area and estimated strength at the 66% radius. Muscle cross-sectional area was 15% lower in the third tertile compared with the first, along with higher fasting insulin concentrations (27%) and homeostasis model of assessment estimate of insulin resistance (31%). Higher RBC AA status aligns with deficits in forearm bone mass, geometry, and muscle mass in children with excess adiposity and early signs of insulin resistance. Novelty Higher arachidonic acid status is associated with lower forearm bone mass in children with overweight condition or obesity. Children with higher arachidonic acid status had increased fasting insulin concentrations and indices of insulin resistance.

Update on bone fragility in spina bifida.

Patients with spina bifida (SB) are at risk for pathological fractures and low bone mineral density (BMD). This article reviews the literature and provides a comprehensive overview of how the characteristics of SB and its associated comorbidities intersect with bone fragility to identify possible pathophysiological mechanisms of fractures and low BMD. Bone fragility occurs early in the life of patients with SB as a result of a disturbance that determines changes in bone shape, quantity, and quality, as poor mineralization reduces bone stiffness. Bone fragility in SB occurs due to local and systemic factors and may be considered a state of impaired bone quality of multifactorial aetiology, with complex interacting influences of neurological, metabolic, and endocrinological origins and the presence of smaller bones. Bone fragility should be evaluated globally according to skeletal age and Tanner staging. The phases of the evolution of Charcot joints seem to intercept the evolution of epiphyseal fractures. Charcot arthropathy in SB may be initiated by the occurrence of repetitive trauma and fractures in epiphyseal and subepiphyseal regions, where there is a deficit of bone mineralization and greater bone mass deficits. Bone fragility in MMC potentially has a multifactorial neuro-endocrinological-metabolic-renal dimension, with smaller bones, lower bone mass, and mineralization deficits affecting bone strength.

Age-dependent bone loss and recovery during hindlimb unloading and subsequent reloading in rats

BackgroundBone structure and strength are rapidly lost during conditions of decreased mechanical loading, and aged bones have a diminished ability to adapt to increased mechanical loading. This is a concern for older patients that experience periods of limited mobility or bed rest, but the acute effects of disuse on the bones of aged patients have not been thoroughly described. Previous animal studies have primarily examined the effect of mechanical unloading on young animals. Those that have studied aged animals have exclusively focused on bone loss during unloading and not bone recovery during subsequent reloading. In this study, we investigated the effect of decreased mechanical loading and subsequent reloading on bone using a hindlimb unloading model in Adult (9 month old) and Aged (28 month old) male rats.MethodsAnimals from both age groups were subjected to 14 days of hindlimb unloading followed by up to 7 days of reloading. Additional Aged rats were subjected to 7 days of forced treadmill exercise during reloading or a total of 28 days of reloading. Trabecular and cortical bone structure of the femur were quantified using ex vivo micro-computed tomography (μCT), and mechanical properties were quantified with mechanical testing.ResultsWe found that Adult rats had substantially decreased trabecular bone volume fraction (BV/TV) following unloading (− 27%) while Aged animals did not exhibit significant bone loss following unloading. However, Aged animals had lower trabecular BV/TV after 3 days of reloading (− 20% compared to baseline), while trabecular BV/TV of Adult rats was not different from baseline values after 3 days of reloading. Trabecular BV/TV of Aged animals remained lower than control animals even with exercise during 7 days of reloading and after 28 days of reloading.ConclusionsThese data suggest that aged bone is less responsive to both increased and decreased mechanical loading, and that acute periods of disuse may leave older subjects with a long-term deficit in trabecular bone mass. These finding indicate the need for therapeutic strategies to improve the skeletal health of elderly patients during periods of disuse.

Gut-derived serotonin contributes to bone deficits in colitis

Osteoporosis and bone fractures occur at higher frequency in patients with inflammatory bowel disease (IBD), and decreased bone mass is observed in animal models of colitis. Another consistent feature of colitis is increased serotonin (5-HT) availability in the intestinal mucosa. Since gut-derived 5-HT can decrease bone mass, via activation of 5-HT1B receptors on pre-osteoblasts, we tested the hypothesis that 5-HT contributes to bone loss in colitis. Colitis was chronically induced in mice by adding dextran sodium sulfate (DSS) to their drinking water for 21 days. At day 21, circulating 5-HT levels were elevated in DSS-inflamed mice. Micro-computed tomography of femurs showed a decrease in trabecular bone volume fraction, formation, and surface area, due largely to decreased trabecular numbers in DSS-treated mice. The colitis-induced loss of trabecular bone was significantly suppressed in mice treated with the 5-HT synthesis inhibitor, p-chloro-DL-phenylalanine (PCPA; 300 mg/kg/day IP daily), and in mice treated with the 5-HT1B receptor antagonist GR55562 (1 mg/Kg/day SC daily). The 5-HT reuptake transporter (SERT) is critical for moving 5-HT from the interstitial space into enterocytes and from serum into platelets. Mice lacking SERT exhibited significant deficits in trabecular bone mass that are similar to those observed in DSS-inflamed mice, and these deficits were not extensively worsened by DSS-induced colitis in the SERT−/− mice. Taken together, findings from both the DSS and SERT−/− mouse models support a contributing role for 5-HT as a significant factor in bone loss induced by colitis.

Structural and functional properties of bone are compromised in amyotrophic lateral sclerosis mice

In addition to muscle weakness, amyotrophic lateral sclerosis (ALS) is associated with an increased incidence of skeletal fractures. The SOD1G93A mouse model recapitulates many features of human ALS. These mice also exhibit decreased bone mass. However, the functional, or biomechanical, behavior of the skeleton in SOD1G93A mice has not been investigated. To do so, we examined skeletal phenotypes in end-stage (16-week-old) SOD1G93A female mice and healthy littermate female controls (N = 9–10/group). Outcomes included trabecular and cortical bone microarchitecture by microcomputed tomography; stiffness and strength via three-point bending; resistance to crack growth by fracture toughness testing; and cortical bone matrix properties via cyclic reference point indentation. SOD1G93A mice had similar bone size, but significantly lower trabecular bone mass (–54%), thinner trabeculae (–41%) and decreased cortical bone thickness (–17%) and cortical area (–18%) compared to control mice (all p < 0.01). In line with these bone mass and microstructure deficits, SOD1G93A mice had significantly lower femoral bending stiffness (–27%) and failure moment (–41%), along with decreased fracture toughness (–18%) (all p < 0.001). This is the first study to demonstrate functional deficits in the skeleton of end-stage ALS mice, and imply multiple mechanisms for increased skeletal fragility and fracture risk in patients in ALS. Importantly, our results provide strong rationale for interventions to reduce fracture risk in ALS patients with advanced disease.

Breech presentation is associated with neonatal and early childhood deficits in bone mass and size

Breech presentation is associated with neonatal and early childhood deficits in bone mass and size

Inflammatory Bowel Disease: Effects on Bone and Mechanisms.

Inflammatory bowel disease (IBD) is associated with decreased bone mass and alterations in bone geometry from the time of diagnosis, before anti-inflammatory therapy is instituted. Deficits in bone mass can persist despite absence of symptoms of active IBD. The effects of IBD on the skeleton are complex. Protein-calorie malnutrition, inactivity, hypogonadism, deficits in calcium intake and vitamin D consumption and synthesis, stunted growth in children, decreased skeletal muscle mass, and inflammation all likely play a role. Preliminary studies suggest that the dysbiotic intestinal microbial flora present in IBD may also affect bone at a distance. Several mechanisms are possible. T cells activated by the gut microbiota may serve as "inflammatory shuttles" between the intestine and bone. Microbe-associated molecular patterns leaked into the circulation in IBD may activate immune responses in the bone marrow by immune cells and by osteocytes, osteoblasts, and osteoclasts that lead to decreased bone formation and increased resorption. Finally, intestinal microbial metabolites such as H2S may also affect bone cell function. Uncovering these mechanisms will enable the design of microbial cocktails to help restore bone mass in patients with IBD.

Effects of a moderately high-protein diet and interval aerobic training combined with strength-endurance exercise on markers of bone metabolism, microarchitecture and turnover in obese Zucker rats

BackgroundWeight loss is a public health concern in obesity-related diseases such as metabolic syndrome, and the protein level of the diets seem to be crucial for the development and maintenance of bone. The nature of exercise and whether exercise in combination with moderately high-protein dietary interventions could protect against potential bone mass deficits remains unclear. ObjectivesTo investigate the effects of a moderately high-protein diet and interval aerobic training combined with strength-endurance exercise (IASE) protocol on bone status, and to assess potential interaction effects (i.e. diet*IASE). MethodsMale Zucker fatty rats were randomized distributed into 4 groups (n=8): normoprotein+sedentary; normoprotein+exercise; moderately high-protein+sedentary, and moderately high-protein+exercise. Training groups conducted an IASE program, 5days/week for 2months. Markers of bone metabolism were measured in plasma. Parameters of bone mass and 3D outcomes for trabecular and cortical bone microarchitecture were assessed by micro-computed tomography. ResultsFemur length, plasma osteocalcin, sclerostin, osteoprotegerin, receptor activator of nuclear factor kappa-B ligand, insulin, leptin, PTH, uric acid and urinary phosphorus levels were lower in the moderately high-protein compared to the normoprotein groups (all, p<0.05), whereas plasma alkaline phosphatase, aspartate aminotransferase, alanine transaminase, and urinary uric acid concentrations, and cortical total volume (TV) and bone volume (BV) were higher in the moderately high-protein (all, p<0.01). Final body weight and alkaline phosphatase levels were lower in the exercise compared to the sedentary (both, p<0.05), whereas femur length and weight, aminoterminal propeptides of type I procollagen and C-terminal telopeptides of type I collagen concentrations, and cortical TV and BV were higher in the exercise compared to the sedentary groups (all, p<0.05). ConclusionThe combination of interventions may be effective to enhance trabecular bone microarchitecture and BMD, and has a partial impact on cortical bone in obese rats. Nevertheless, they do not induce any alteration on the bone turnover markers.

Lower bone turnover and relative bone deficits in men with metabolic syndrome: a matter of insulin sensitivity? The European Male Ageing Study.

Metabolic syndrome (MetS) has been associated with lower bone turnover and relative bone mass or strength deficits (i.e. not proportionate to body mass index, BMI), but the relative contributions of MetS components related to insulin sensitivity or obesity to male bone health remain unclear. We determined cross-sectional associations of MetS, its components and insulin sensitivity (by homeostatic model assessment-insulin sensitivity (HOMA-S)) using linear regression models adjusted for age, centre, smoking, alcohol, and BMI. Bone turnover markers and heel broadband ultrasound attenuation (BUA) were measured in 3129 men aged 40-79. Two centres measured total hip, femoral neck, and lumbar spine areal bone mineral density (aBMD, n = 527) and performed radius peripheral quantitative computed tomography (pQCT, n = 595). MetS was present in 975 men (31.2%). Men with MetS had lower β C-terminal cross-linked telopeptide (β-CTX), N-terminal propeptide of type I procollagen (PINP) and osteocalcin (P < 0.0001) and higher total hip, femoral neck, and lumbar spine aBMD (P ≤ 0.03). Among MetS components, only hypertriglyceridaemia and hyperglycaemia were independently associated with PINP and β-CTX. Hyperglycaemia was negatively associated with BUA, hypertriglyceridaemia with hip aBMD and radius cross-sectional area (CSA) and stress-strain index. HOMA-S was similarly associated with PINP and β-CTX, BUA, and radius CSA in BMI-adjusted models. Men with MetS have higher aBMD in association with their greater body mass, while their lower bone turnover and relative deficits in heel BUA and radius CSA are mainly related to correlates of insulin sensitivity. Our findings support the hypothesis that underlying metabolic complications may be involved in the bone's failure to adapt to increasing bodily loads in men with MetS.