Showing papers on "Bone density published in 2016"
TL;DR: Among postmenopausal women with osteoporosis, the use of subcutaneous abaloparatide, compared with placebo, reduced the risk of new vertebral and nonvertebral fractures over 18 months.
Abstract: Importance Additional therapies are needed for prevention of osteoporotic fractures. Abaloparatide is a selective activator of the parathyroid hormone type 1 receptor. Objective To determine the efficacy and safety of abaloparatide, 80 μg, vs placebo for prevention of new vertebral fracture in postmenopausal women at risk of osteoporotic fracture. Design, Setting, and Participants The Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE) was a phase 3, double-blind, RCT (March 2011-October 2014) at 28 sites in 10 countries. Postmenopausal women with bone mineral density (BMD) T score ≤−2.5 and >−5.0 at the lumbar spine or femoral neck and radiological evidence ≥2 mild or ≥1 moderate lumbar or thoracic vertebral fracture or history of low-trauma nonvertebral fracture within the past 5 years were eligible. Postmenopausal women (>65 y) with fracture criteria and a T score ≤−2.0 and >−5.0 or without fracture criteria and a T score ≤−3.0 and >−5.0 could enroll. Interventions Blinded, daily subcutaneous injections of placebo (n = 821); abaloparatide, 80 μg (n = 824); or open-label teriparatide, 20 μg (n = 818) for 18 months. Main Outcomes and Measures Primary end point was percentage of participants with new vertebral fracture in the abaloparatide vs placebo groups. Sample size was set to detect a 4% difference (57% risk reduction) between treatment groups. Secondary end points included change in BMD at total hip, femoral neck, and lumbar spine in abaloparatide-treated vs placebo participants and time to first incident nonvertebral fracture. Hypercalcemia was a prespecified safety end point in abaloparatide-treated vs teriparatide participants. Results Among 2463 women (mean age, 69 years [range, 49-86]), 1901 completed the study. New morphometric vertebral fractures occurred in 0.58% (n = 4) of the abaloparatide group, 4.22% (n = 30) of the placebo group (risk difference [RD] vs placebo, −3.64 [95% CI, −5.42 to −2.10]; relative risk, 0.14 [95% CI, 0.05-0.39]; P P = .049), and 3.3% for teriparatide. BMD increases were greater with abaloparatide than with placebo (all P P = .006). Conclusions and Relevance Among postmenopausal women with osteoporosis, the use of subcutaneous abaloparatide, compared with placebo, reduced the risk of new vertebral and nonvertebral fractures over 18 months. Further research is needed to understand the clinical importance of RD, the risks and benefits of abaloparatide treatment, and the efficacy of abaloparatide vs other osteoporosis treatments. Trial Registration clinicaltrials.gov Identifier:NCT01343004
748 citations
TL;DR: This review will define the role of collagen and within-bone heterogeneity and elaborate the importance of trabecular and cortical architecture with regard to their effect on the mechanical strength of bone.
Abstract: This review will define the role of collagen and within-bone heterogeneity and elaborate the importance of trabecular and cortical architecture with regard to their effect on the mechanical strength of bone. For each of these factors, the changes seen with osteoporosis and ageing will be described and how they can compromise strength and eventually lead to bone fragility.
469 citations
TL;DR: In older patients with T2DM, canagliflozin showed small but significant reductions in total hip BMD and increases in bone formation and resorption biomarkers, due at least in part to weight loss.
Abstract: Context: Canagliflozin is a sodium glucose cotransporter 2 inhibitor developed to treat type 2 diabetes mellitus (T2DM). Objective: Our objective is to describe the effects of canagliflozin on bone mineral density (BMD) and bone biomarkers in patients with T2DM. Design: This was a randomized study, consisting of a 26-week, double-blind, placebo-controlled period and a 78-week, double-blind, placebo-controlled extension. Setting: This study was undertaken in 90 centers in 17 countries. Patients: Patients were aged 55–80 years (N = 716) and whose T2DM was inadequately controlled on a stable antihyperglycemic regimen. Interventions: Canagliflozin 100 or 300 mg or placebo were administered once daily. Outcome and Measures: BMD was assessed using dual-energy x-ray absorptiometry at weeks 26, 52, and 104. Bone strength was assessed using quantitative computed tomography and finite element analysis at week 52. Serum collagen type 1 β-carboxy-telopeptide, osteocalcin, and estradiol were assessed at weeks 26 and 5...
255 citations
TL;DR: It is demonstrated that dual inhibition of sclerostin and DKK-1 leads to synergistic bone formation in rodents and non-human primates, and by targeting distinct facets of fracture healing, the bispecific antibody shows superior bone repair activity compared with monotherapies.
Abstract: Inhibition of the Wnt antagonist sclerostin increases bone mass in patients with osteoporosis and in preclinical animal models. Here we show increased levels of the Wnt antagonist Dickkopf-1 (DKK-1) in animals treated with sclerostin antibody, suggesting a negative feedback mechanism that limits Wnt-driven bone formation. To test our hypothesis that co-inhibition of both factors further increases bone mass, we engineer a first-in-class bispecific antibody with single residue pair mutations in the Fab region to promote efficient and stable cognate light-heavy chain pairing. We demonstrate that dual inhibition of sclerostin and DKK-1 leads to synergistic bone formation in rodents and non-human primates. Furthermore, by targeting distinct facets of fracture healing, the bispecific antibody shows superior bone repair activity compared with monotherapies. This work supports the potential of this agent both for treatment and prevention of fractures and offers a promising therapeutic approach to reduce the burden of low bone mass disorders.
237 citations
TL;DR: Clinicians should be aware that BMD measurements underestimate fracture risk in people with type 2 diabetes, and that new treatments for diabetes, with neutral or positive effects on skeletal health, might play a part in the management of diabetes in those at high risk of fracture.
216 citations
TL;DR: The evidence is presented for impaired nutrition, hormonal dysfunction, and low bone mineral density in a subset of male athletes, and how these health issues may parallel those of the Triad, and evidence-based guidelines can be developed that result in best practice.
Abstract: Participation in sports offers many health benefits to athletes of both sexes. However, subsets of both female and male athletes are at increased risk of impaired bone health and bone stress injuries. The Female Athlete Triad (Triad) is defined as the interrelationship of low energy availability (with or without disordered eating), menstrual dysfunction, and low bone mineral density. The Triad may result in health consequences, including bone stress injuries. Our review presents evidence that an analogous process may occur in male athletes. Our review of the available literature indicates that a subset of male athletes may experience adverse health issues that parallel those associated with the Triad, including low energy availability (with or without disordered eating), hypogonadotropic hypogonadism, and low bone mineral density. Consequently, male athletes may be predisposed to developing bone stress injuries, and these injuries can be the first presenting feature of associated Triad conditions. We discuss the evidence for impaired nutrition, hormonal dysfunction, and low bone mineral density in a subset of male athletes, and how these health issues may parallel those of the Triad. With further research into the mechanisms and outcomes of these health concerns in active and athletic men, evidence-based guidelines can be developed that result in best practice.
195 citations
TL;DR: This Review examines the evolution of the field of osteoimmunology and how advances in understanding of the ISI might lead to novel approaches to prevent and treat bone loss, and avert fractures.
Abstract: Osteoporosis develops when the rate of osteoclastic bone breakdown (resorption) exceeds that of osteoblastic bone formation, which leads to loss of BMD and deterioration of bone structure and strength. Osteoporosis increases the risk of fragility fractures, a cause of substantial morbidity and mortality, especially in elderly patients. This imbalance between bone formation and bone resorption is brought about by natural ageing processes, but is frequently exacerbated by a number of pathological conditions. Of importance to the aetiology of osteoporosis are findings over the past two decades attesting to a deep integration of the skeletal system with the immune system (the immuno-skeletal interface (ISI)). Although protective of the skeleton under physiological conditions, the ISI might contribute to bone destruction in a growing number of pathophysiological states. Although numerous research groups have investigated how the immune system affects basal and pathological osteoclastic bone resorption, recent findings suggest that the reach of the adaptive immune response extends to the regulation of osteoblastic bone formation. This Review examines the evolution of the field of osteoimmunology and how advances in our understanding of the ISI might lead to novel approaches to prevent and treat bone loss, and avert fractures.
193 citations
TL;DR: Assessment of the sagittal view alone at routine abdominal CT for both vertebral fractures and trabecular bone mineral density provides a rapid and effective opportunistic screen for detecting individuals at increased risk for fragility fractures.
Abstract: Opportunistic osteoporosis screening using abdominal CT scans obtained for other purposes has the potential to increase detection of those at increased risk for fragility fractures. We sought to combine the tasks of density measurement and vertebral fracture assessment on the sagittal view. We confirm that this represents a robust approach and recommend its implementation in clinical practice. Opportunistic osteoporosis screening at routine abdominal CT has been proposed by measuring axial (transverse) L1 trabecular attenuation and by sagittal reconstruction for vertebral fracture assessment. We sought to combine this dual evaluation on the sagittal reconstruction alone to improve efficiency. Routine contrast-enhanced abdominal CT scans performed for any indication on 571 consecutive adults age 60 years or older (mean age 70.7 years) were retrospectively analyzed. These were performed at a single center over a 3-month period. L1 trabecular attenuation was measured using an ovoid region-of-interest on both the transverse and sagittal series. The sagittal reconstruction was also analyzed for moderate-to-severe vertebral compression fractures using the Genant visual semi-quantitative method. Likely osteoporosis was defined by a moderate-to-severe fracture and/or sagittal L1 trabecular attenuation of ≤110 Hounsfield units (HU) (previously found to be >90 % specific for osteoporosis on our calibrated GE CT scanners at 120 kVp). Correlation was made with hip and spine dual X-ray absorptiometry (DXA). Mean absolute difference in L1 trabecular attenuation between transverse and sagittal reconstructions was 6.7 HU (±5.7) or 6.2 %. The transverse and sagittal HU measurements were in agreement (i.e., both measurements above or below this threshold) in 94.5 % of cases at the 110-HU cutoff. A total of 243 (42.3 %) patients had likely osteoporosis by CT criteria, of which only 48 (19.8 %) had previous DXA screening. Assessment of the sagittal view alone at routine abdominal CT for both vertebral fractures and trabecular bone mineral density provides a rapid and effective opportunistic screen for detecting individuals at increased risk for fragility fractures.
184 citations
TL;DR: It is widely acknowledged that obesity is positively associated to many chronic disorders such as metabolic syndrome, dyslipidemia and type 2 diabetes, conditions that could themselves affect bone health, but little is yet known on the mechanisms via which obesity and its comorbidities may contribute to such damage.
Abstract: Recent evidence demonstrating an increased fracture risk among obese individuals suggests that adipose tissue may negatively impact bone health, challenging the traditional paradigm of fat mass playing a protective role towards bone health. White adipose tissue, far from being a mere energy depot, is a dynamic tissue actively implicated in metabolic reactions, and in fact secretes several hormones called adipokines and inflammatory factors that may in turn promote bone resorption. More specifically, Visceral Adipose Tissue (VAT) may potentially prove detrimental. It is widely acknowledged that obesity is positively associated to many chronic disorders such as metabolic syndrome, dyslipidemia and type 2 diabetes, conditions that could themselves affect bone health. Although aging is largely known to decrease bone strength, little is yet known on the mechanisms via which obesity and its comorbidities may contribute to such damage. Given the exponentially growing obesity rate in recent years and the increased life expectancy of western countries it appears of utmost importance to timely focus on this topic.
172 citations
TL;DR: In patients with osteoporosis at high risk for fracture, the full continuous 24-month course with teriparatide results in improved skeletal health and outcomes than shorter time periods.
Abstract: Teriparatide (TPTD) is the only currently available therapeutic agent that increases the formation of new bone tissue and can provide some remediation of the architectural defects in the osteoporotic skeleton. The use of teriparatide clinically is limited to 24 months. We review clinical findings during daily teriparatide treatment over time. Teriparatide appears to increase bone formation more than bone resorption as determined biochemically and histologically. Teriparatide exerts its positive effects on bone formation in two distinct fashions. The first is direct stimulation of bone formation that occurs within active remodeling sites (remodeling-based bone formation) and on surfaces of bone previously inactive (modeling-based bone formation). The second is an increase in the initiation of new remodeling sites. Both processes contribute to the final increase in bone density observed by non-invasive tools such as DXA. Remodeling is the repair process by which skeletal tissue is maintained in a young healthy state, and when stimulated by TPTD is associated with a positive bone balance within each remodeling cavity. It seems likely therefore that this component will contribute to the anti-fracture efficacy of TPTD. Teriparatide reduces the risk of fracture, and this effect appears to increase with longer duration of therapy. The use of novel treatment regimens, including shorter courses, should be held in abeyance until controlled clinical trials are completed to define the relative fracture benefits of such approaches in comparison to the 24-month daily use of the agent.
169 citations
TL;DR: The developing scientific knowledge regarding the epidemiology and pathophysiology of skeletal fragility in patients with diabetes and the emerging data on the prediction, treatment, and outcomes of fractures in individuals with type 1 and type 2 diabetes are assessed.
Abstract: Fracture risk is significantly increased in both type 1 and type 2 diabetes, and individuals with diabetes experience worse fracture outcomes than normoglycemic individuals. Factors that increase fracture risk include lower bone mass in type 1 diabetes and compromised skeletal quality and strength despite preserved bone density in type 2 diabetes, as well as the effects of comorbidities such as diabetic macro- and microvascular complications. In this Perspective, we assess the developing scientific knowledge regarding the epidemiology and pathophysiology of skeletal fragility in patients with diabetes and the emerging data on the prediction, treatment, and outcomes of fractures in individuals with type 1 and type 2 diabetes.
TL;DR: Osseodensification technique used in the present in vivo study was demonstrated to be able to increase the %BV around dental implants inserted in low-density bone in respect to conventional implant drilling techniques, which may play a role in enhancing implant stability and reduce micromotion.
Abstract: Purpose:The aim of this study was to evaluate a new surgical technique for implant site preparation that could allow to enhance bone density, ridge width, and implant secondary stability.Materials and Methods:The edges of the iliac crests of 2 sheep were exposed and ten 3.8 × 10-mm Dynamix implants
TL;DR: BMD was significantly decreased, while bone turnover was elevated, and bone remodeling was accelerated following bariatric surgery, suggesting that calcium and vitamin D should be monitored closely and supplemented accordingly after the surgery.
Abstract: The aim is to evaluate via meta-analysis bone metabolism and bone mineral density (BMD) in morbidly obese patients before and after bariatric surgery. We searched Medline, EMBASE, and the Cochrane Library for relevant studies published before January 2014. The following outcomes were evaluated: serum calcium, serum parathyroid hormone (PTH), serum 25-hydroxyvitamin D [25(OH)D], serum or urinary N-telopeptide (NTX), bone-specific alkaline phosphatase (BSAP), and bone mineral density (BMD). Ten studies, including 344 patients, met our inclusion criteria. Results showed a significant decrease in serum calcium (MD = −0.10, 95 %CI −0.14 to −0.07, P < 0.00001) and increase in serum PTH (MD = 12.41, 95 %CI 6.51 to 18.31, P < 0.00001) but no significant difference in serum 25(OH)D (MD = 1.35, 95 %CI −1.12 to 3.83, P = 0.28) following bariatric surgery. There were significant increases in serum or urinary NTX (MD = 18.49, 95 %CI 3.33 to 33.66, P = 0.02) and BSAP (MD = 7.47, 95 %CI 0.21 to 14.72, P = 0.04) but a significant decrease in BMD (MD = −0.08, 95 %CI −0.13 to −0.04, P < 0.00001) after bariatric surgery. BMD was significantly decreased, while bone turnover was elevated, and bone remodeling was accelerated following bariatric surgery. Basal bone metabolism should be evaluated preoperatively. To prevent secondary hyperparathyroidism and bone loss, calcium and vitamin D should be monitored closely and supplemented accordingly after the surgery.
TL;DR: Increasing physical activity in children with diabetes as well as good glycaemic control appears to provide some improvement of bone parameters, although robust clinical studies are still lacking.
Abstract: Subjects with type 1 diabetes mellitus (T1DM) have decreased bone mineral density and an up to sixfold increase in fracture risk. Yet bone fragility is not commonly regarded as another unique complication of diabetes. Both animals with experimentally induced insulin deficiency syndromes and patients with T1DM have impaired osteoblastic bone formation, with or without increased bone resorption. Insulin/IGF1 deficiency appears to be a major pathogenetic mechanism involved, along with glucose toxicity, marrow adiposity, inflammation, adipokine and other metabolic alterations that may all play a role on altering bone turnover. In turn, increasing physical activity in children with diabetes as well as good glycaemic control appears to provide some improvement of bone parameters, although robust clinical studies are still lacking. In this context, the role of osteoporosis drugs remains unknown.
TL;DR: Lower 25(OH)D may not reflect at-risk skeletal health in obese people, and BMI should be considered when interpreting serum 25( OH)D as a marker of vitamin D status.
TL;DR: Sarcopenic and dynapenic obese older adults may have increased risk of osteoporosis and non-vertebral fracture relative to obese alone counterparts and potentially represent a subset of the obese older adult population who require closer monitoring of bone health during ageing.
Abstract: The purpose of this study is to determine whether low muscle mass (sarcopenia) or strength (dynapenia), in the presence of obesity, are associated with increased risk for osteoporosis and non-vertebral fracture over 5-10 years in community-dwelling older adults. N = 1089 volunteers (mean ± SD age 62 ± 7 years; 51 % female) participated at baseline and 761 attended follow-up clinics (mean 5.1 ± 0.5 years later). Total body, total hip and spine BMD, and appendicular lean and total fat mass were assessed by DXA. Sarcopenic obesity and dynapenic obesity were defined as the lowest sex-specific tertiles for appendicular lean mass or lower-limb strength, respectively, and the highest sex-specific tertile for total fat mass. Fractures were self-reported on three occasions over 10.7 ± 0.7 years in 563 participants. Obese alone participants had significantly higher BMD at all sites compared with non-sarcopenic non-obese. Sarcopenic obese and dynapenic obese men had lower spine and total body BMD, respectively, and sarcopenic obese women had lower total hip BMD, compared with obese alone (all P < 0.05). Sarcopenic obese men had higher non-vertebral fracture rates compared to non-sarcopenic non-obese (incidence rate ratio: 3.0; 95 % CI 1.7-5.5), and obese alone (3.6; 1.7-7.4). Sarcopenic obese women had higher fracture rates compared with obese alone (2.8; 1.4-5.6), but this was non-significant after adjustment for total hip BMD. Sarcopenic and dynapenic obese older adults may have increased risk of osteoporosis and non-vertebral fracture relative to obese alone counterparts. Sarcopenic and dynapenic obese individuals potentially represent a subset of the obese older adult population who require closer monitoring of bone health during ageing.
TL;DR: Prophylactic teriparatide treatment improved the volumetric BMD and fine bone structure at UIV+1 and reduced the PJK-type 2 incidence.
Abstract: We conducted a prospective comparative study of the effect of teriparatide therapy for preventing vertebral-failure-type PJK after reconstructive surgery for adult spinal deformity. Prophylactic teriparatide improved the volumetric bone mineral density and fine bone structure of the vertebra above the upper-instrumented vertebra and reduced the incidence of vertebral-failure-type PJK. Proximal junctional kyphosis (PJK) is a complication after corrective surgery for spinal deformity. This study sought to determine whether teriparatide (TP) is an effective prophylactic against PJK type 2 (vertebral fracture) in surgically treated patients with adult spinal deformity (ASD). Forty-three patients who started TP therapy immediately after surgery and 33 patients who did not receive TP were enrolled in this prospective case series. These patients were female, over 50, surgically treated for ASD, and followed for at least 2 years. Preoperative and postoperative standing whole-spine X-rays and dual-energy X-ray absorptiometry scans, and multidetector CT images obtained before and 6 months after surgery were used to analyze the bone strength in the vertebra above the upper-instrumented vertebra (UIV+1). Mean age was 67.9 years. After 6 months of treatment, mean hip-bone mineral density (BMD) increased from 0.721 to 0.771 g/cm2 in the TP group and decreased from 0.759 to 0.729 g/cm2 in the control group. This percent BMD change between groups was significant (p < 0.05). The volumetric BMD (326 to 366 mg/cm3) and bone mineral content (BMC) (553 to 622 mg) at UIV+1 were also significantly increased in TP group. The bone volume/tissue volume ratio increased from 46 to 54 % in the TP group, and the trabecular bone thickness and number increased by 14 and 5 %, respectively. At the 2-year follow-up, the PJK type 2 incidence was significantly lower in the TP group (4.6 %) than in the control group (15.2 %; p = .02). Prophylactic TP treatment improved the volumetric BMD and fine bone structure at UIV+1 and reduced the PJK-type 2 incidence.
TL;DR: Evidence suggests that the safest and most effective strategy to improve bone health in AN is normalization of weight with restoration of menses, and Pharmacotherapies that show promise include physiologic estradiol replacement (as the transdermal estradio patch), and in adults, bisphosphonates.
Abstract: Objective
Low bone mineral density (BMD) is a known consequence of anorexia nervosa (AN) and is particularly concerning during adolescence, a critical time for bone accrual. A comprehensive synthesis of available data regarding impaired bone health, its determinants, and associated management strategies in AN is currently lacking. This systematic review aims to synthesize information from key physiologic and prospective studies and trials, and provide a thorough understanding of impaired bone health in AN and its management.
Method
Search terms included “anorexia nervosa” AND “bone density” for the period 1995–2015, limited to articles in English. Papers were screened manually based on journal impact factor, sample size, age of participants, and inclusion of a control group. When necessary, we included seminal papers published before 1995.
Results
AN leads to low BMD, impaired bone quality and increased fracture risk. Important determinants are low lean mass, hypogonadism, IGF-1 deficiency, and alterations in other hormones that impact bone health. Weight gain and menses restoration are critical for improving bone outcomes in AN. Physiologic estrogen replacement as the transdermal patch was shown to increase bone accrual in one study in adolescent females with AN; however, residual deficits persist. Bisphosphonates are potentially useful in adults with AN.
Discussion
To date, evidence suggests that the safest and most effective strategy to improve bone health in AN is normalization of weight with restoration of menses. Pharmacotherapies that show promise include physiologic estradiol replacement (as the transdermal estradiol patch), and in adults, bisphosphonates. Further studies are necessary to determine the best strategies to normalize BMD in AN.
TL;DR: For the cases examined, the effect of stress shielding on the periprosthetic bone seems to be more significantly influenced by the implant material than by the implants geometry.
TL;DR: Treatment with Scl-Ab prevented GC-induced reduction in both trabecular and cortical bone mass and strength and appeared to maintain osteoblast activity through autophagy.
Abstract: Summary
This study was to determine if antibody against sclerostin (Scl-Ab) could prevent glucocorticoid (GC)-induced osteoporosis in mice We found that Scl-Ab prevented GC-induced reduction in bone mass and bone strength and that the anabolic effects of Scl-Ab might be partially achieved through the preservation of osteoblast activity through autophagy
TL;DR: Two years of combined teriparatide and denosumab improves bone microarchitecture and estimated strength more than the individual treatments, particularly in cortical bone.
Abstract: Context: In postmenopausal osteoporosis, combining denosumab and teriparatide increases hip and spine bone mineral density more than either monotherapy. Objective: The objective of the study was to determine the effects of 2 years of combination therapy on bone microarchitecture and estimated strength. Design: This was an open-label, randomized controlled trial. Participants and Methods: We performed high-resolution peripheral quantitative computed tomography at the distal tibia and radius in 94 postmenopausal osteoporotic women randomized to 2 years of teriparatide 20 μg sc daily, denosumab 60 mg sc every 6 months, or both. Results: Total volumetric bone mineral density (vBMD) at the radius and tibia, trabecular vBMD at the radius, and cortical vBMD at the tibia all increased more in the combination group than both monotherapy groups (P < .002 for all comparisons with combination). Cortical thickness at the tibia also increased more in the combination group (8.1% ± 4.3%) than both other groups (P < .001)...
TL;DR: The data reveals a previously unappreciated effect of a mild surgical procedure causing a long-lasting effect on inflammatory gene expression in the gut and the bone and demonstrates that in intact female mice, the beneficial effect of L. reuteri on bone requires an elevated inflammatory status.
Abstract: Background & Aims
We previously demonstrated that short-term oral administration of the probiotic Lactobacillus reuteri 6475 enhanced bone density in male but not female mice. We also established that L. reuteri 6475 enhanced bone health and prevented bone loss in estrogen-deficient female mice. In this study, we tested whether a mild inflammatory state and/or a long-term treatment with the probiotic was required to promote a positive bone effect in estrogen-sufficient female mice.
TL;DR: Systemic BMD in patients with early RA is reduced in relation with ACPA positivity and high RF levels, which supports the notion that RA-associated autoimmunity may have a direct causative role in bone remodeling.
Abstract: Autoantibodies such as anti-citrullinated protein antibodies (ACPA) are major risk factors for articular bone destruction from the earliest phases of rheumatoid arthritis (RA). The aim of the current study was to determine whether RA-associated autoantibodies also impact on systemic bone loss in patients with early disease. Systemic bone mineral density (BMD) was measured in the lumbar spine and the hip in 155 consecutive treatment-naive patients with early RA (median symptom duration 13 weeks). Demographic and disease-specific parameters, including clinical disease activity, ultrasonographic (US) examination of the hands and wrists, radiographic scoring of joint damage, ACPA and rheumatoid factor (RF) levels were recorded from all patients. Reduced BMD was defined as Z score ≤ -1 SD and analysed in relation to disease-related characteristics and autoantibody subgroups. Reduced BMD was found in 25.5 % of the patients in the spine and 19.4 % in the hip. Symptom duration, clinical and US disease activity, functional disability and radiographic damage did not significantly impact on spine and hip BMD loss in regression analyses adjusted for possible confounders (age, gender, menopausal status, current smoking, body mass index). In contrast, ACPA positivity (at any level) negatively affected the spine Z-score (adjusted OR (95 % CI) 2.76 (1.19 to 6.42)); the hip Z score was affected by high titres only (adjusted OR (95 % CI) 2.96 (1.15 to 7.66)). The association of ACPA with reduced BMD in the spine was confirmed even at low levels of RF (adjusted OR (95 % CI) 2.65 (1.01 to 7.24)), but was further increased by concomitant high RF (adjusted OR (95 % CI) 3.38 (1.11 to 10.34)). In contrast, Z scores in the hip were significantly reduced only in association with high ACPA and RF (adjusted OR (95 % CI) 4.96 (1.48 to 16.64)). Systemic BMD in patients with early RA is reduced in relation with ACPA positivity and high RF levels. This finding supports the notion that RA-associated autoimmunity may have a direct causative role in bone remodeling.
TL;DR: It is concluded that inflammation may play an important role in the etiology of fractures in older men, after adjusting for appendicular lean mass, disability, and bone density, suggesting mediating roles.
Abstract: Cytokines play major roles in regulating bone remodeling, but their relationship to incident fractures in older men is uncertain. We tested the hypothesis that men with higher concentrations of pro-inflammatory markers have a higher risk of fracture. We used a case-cohort design and measured inflammatory markers in a random sample of 961 men and in men with incident fractures including 120 clinical vertebral, 117 hip, and 577 non-spine fractures; average follow-up 6.13 years (7.88 years for vertebral fractures). We measured interleukin (IL)-6, C-reactive protein (CRP), tumor necrosis factor alpha (TNFα), soluble receptors (SR) of IL-6 (IL-6SR) and TNF (TNFαSR1 and TNFαSR2), and IL-10. The risk of non-spine, hip, and clinical vertebral fracture was compared across quartiles (Q) of inflammatory markers using Cox proportional hazard models with tests for linear trend. In multivariable-adjusted models, men with the highest (Q4) TNFa cytokine concentrations and their receptors had a 2.0-4.2-fold higher risk of hip and clinical vertebral fracture than men with the lowest (Q1). Results were similar for all non-spine fractures, but associations were smaller. There was no association between CRP and IL-6SR and fracture. Men in the highest Q of IL-10 had a 49% lower risk of vertebral fracture compared with men in Q1. Among men with ≥3 inflammatory markers in the highest Q, the hazard ratio (HR) for hip fractures was 2.03 (95% confidence interval [CI] 1.11-3.71) and for vertebral fracture 3.06 (1.66-5.63). The HRs for hip fracture were attenuated by 27%, 27%, and 15%, respectively, after adjusting for appendicular lean mass (ALM), disability, and bone density, suggesting mediating roles. ALM also attenuated the HR for vertebral fractures by 10%. There was no association between inflammation and rate of hip BMD loss. We conclude that inflammation may play an important role in the etiology of fractures in older men. © 2016 American Society for Bone and Mineral Research.
TL;DR: Intradialytic aerobic cycling exercise programs can effectively alleviate inflammation and improve nutrition, bone mineral density, and exercise tolerance in hemodialysis patients.
TL;DR: The association between severe AAC and fracture risk was found in both sexes, mainly in the follow-ups of less than 10years, and further studies are needed to investigate clinical utility of AAC for the assessment of fracture and cardiovascular risk at the individual level.
TL;DR: In this paper, the relationship of parathyroidectomy and bisphosphonates with skeletal outcomes in patients with primary hyperparathyroidism (PHPT) was measured.
Abstract: Background The comparative effectiveness of surgical and medical treatments on fracture risk in primary hyperparathyroidism (PHPT) is unknown. Objective To measure the relationship of parathyroidectomy and bisphosphonates with skeletal outcomes in patients with PHPT. Design Retrospective cohort study. Setting An integrated health care delivery system. Participants All enrollees with biochemically confirmed PHPT from 1995 to 2010. Measurements Bone mineral density (BMD) changes and fracture rate. Results In 2013 patients with serial bone density examinations, total hip BMD increased transiently in women with parathyroidectomy (4.2% at 8 years). In 6272 patients followed for fracture, the absolute risk for hip fracture at 10 years was 20.4 events per 1000 patients who had parathyroidectomy and 85.5 events per 1000 patients treated with bisphosphonates compared with 55.9 events per 1000 patients without these treatments. The risk for any fracture at 10 years was 156.8 events per 1000 patients who had parathyroidectomy and 302.5 events per 1000 patients treated with bisphosphonates compared with 206.1 events per 1000 patients without these treatments. In analyses stratified by baseline BMD status, parathyroidectomy was associated with reduced fracture risk in both osteopenic and osteoporotic patients, whereas bisphosphonates were associated with increased fracture risk in these patients. Parathyroidectomy was associated with fracture risk reduction in patients regardless of whether they satisfied criteria from consensus guidelines for surgery. Limitation Retrospective study design and nonrandom treatment assignment. Conclusion Parathyroidectomy was associated with reduced fracture risk, and bisphosphonate treatment was not superior to observation. Primary funding source National Institute on Aging.
TL;DR: In nondiabetic, postmenopausal women, insulin resistance was associated with smaller bone size, greater volumetric bone mineral density, and generally favorable bone microarchitecture at weight-bearing and nonweight-bearing skeletal sites, suggesting that hyperinsulinemia directly affects bone structure independent of obesity.
Abstract: Context: The clinical consequences of insulin resistance and hyperinsulinemia on bone remain largely unknown. Objective: The objective of the study was to evaluate the effect of insulin resistance on peripheral bone geometry, volumetric bone mineral density (vBMD), bone microarchitecture, and estimated bone strength. Design, Setting, and Participants: This cross-sectional study included 146 postmenopausal, nondiabetic Caucasian women (mean age 60.3 ± 2.7 y) who were participating in the Study of Women's Health Across the Nation. Interventions: There were no interventions. Main Outcome Measures: High-resolution peripheral quantitative computed tomography was used to assess bone density and microstructure at the distal radius and tibia. Fasting insulin and glucose were measured and insulin resistance was estimated using homeostasis model assessment of insulin resistance (HOMA-IR), with higher values indicating greater insulin resistance. Results: There was a negative association between HOMA-IR and bone siz...
TL;DR: Denosumab increased BMD in the first year after kidney transplantation but was associated with more frequent episodes of urinary tract infection and graft function, rate of rejects, and incidence of opportunistic infections were similar.
TL;DR: Obesity is associated with BMD of the hip and lumbar spine and overweight and obese individuals have similar degrees of osteoporosis, which could be an important issue for further investigation.
Abstract: BACKGROUND We investigated whether there were gender differences in the effect of obesity on bone mineral density (BMD) based on menopausal status. METHODS We assessed 5,892 consecutive patients 20 to 91 years old who were referred for dual-energy X-ray absorptiometry (DXA) scans. All subjects underwent a standard BMD scan of the hip (total hip and femoral neck) and lumbar spine (L1 to L4) using a DXA scan and body size assessment. Body mass index was used to categorize the subjects as normal weight, overweight, and obese. RESULTS BMD was higher in obese and overweight versus normal weight men, premenopausal women, and postmenopausal women. Compared to men ≥50 years and postmenopausal women with normal weight, the age-adjusted odds ratio of osteopenia was 0.19 (95% confidence interval [CI], 0.07 to 0.56) and 0.38 (95% CI, 0.29 to 0.51) for obese men ≥50 years and postmenopausal women. Corresponding summaries for osteoporosis were 0.26 (95% CI, 0.11 to 0.64) and 0.15 (95% CI, 0.11 to 0.20), respectively. Compared to men <50 years and premenopausal women with normal weight, the age-adjusted odds ratio of low bone mass was 0.22 (95% CI, 0.11 to 0.45) and 0.16 (95% CI, 0.10 to 0.26) for obese men <50 years and premenopausal women, respectively. CONCLUSION Obesity is associated with BMD of the hip and lumbar spine and overweight and obese individuals have similar degrees of osteoporosis. This result was not significantly different based on gender and menopausal status, which could be an important issue for further investigation.