Lower Hip Bone Mineral Density Research Articles

Effects of Abaloparatide on Bone Mineral Density in Proximal Femoral Regions Corresponding to Arthroplasty Gruen Zones: A Study of Postmenopausal Women with Osteoporosis.

Low hip bone mineral density (BMD) in patients who undergo total hip arthroplasty (THA) increases the risk of periprosthetic fractures, implant instability, and other complications. Recently, emphasis has been placed on bone health optimization: treating low BMD prior to a planned orthopaedic implant procedure in an effort to normalize BMD and reduce the potential risk of future complications. Abaloparatide is a U.S. Food and Drug Administration-approved osteoanabolic agent for men and postmenopausal women with osteoporosis and a candidate drug for bone health optimization that, in addition to benefits at the spine, increases hip BMD and reduces nonvertebral fracture risk. We hypothesized that abaloparatide would improve BMD in proximal femoral regions surrounding a virtual THA stem. This post hoc analysis obtained dual x-ray absorptiometry (DXA) hip scans from 500 randomly selected postmenopausal women with osteoporosis from the Phase-3 Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE, NCT01343004) study after 0, 6, and 18 months of abaloparatide (250 patients) or placebo (250 patients). Hip DXA scans underwent 3-dimensional (3D) modeling via 3D-Shaper, followed by virtual resection of the proximal femur and simulated placement of a tapered, flat-wedge hip stem that guided delineation of the Gruen zones that were fully (zones 1 and 7) or largely (zones 2 and 6) captured in the scanning region. Integral, cortical, and trabecular volumetric BMD, cortical thickness, and cortical surface BMD (the product of cortical volumetric BMD and cortical thickness) were determined for each zone. Compared with placebo, the abaloparatide group showed greater increases in integral volumetric BMD in all zones at months 6 and 18; cortical surface BMD in zones 1, 6, and 7 at month 6; cortical thickness, cortical volumetric BMD, and cortical surface BMD in all zones at month 18; and trabecular volumetric BMD in zones 1 and 7 at months 6 and 18. Abaloparatide increases BMD in proximal femoral regions that interact with and support femoral stems, suggesting that abaloparatide may have value for preoperative or potentially perioperative bone health optimization in patients with osteoporosis undergoing THA. Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Bone mineral density in adults with arthrogryposis multiplex congenita: a retrospective cohort analysis

The primary objective of this study was to evaluate the prevalence of low femoral and lumbar spine bone mineral density (BMD) in adults with arthrogryposis multiplex congenita (AMC). We performed a retrospective cohort analysis of adults with AMC who were enrolled in the French Reference Center for AMC and in the Pediatric and Adult Registry for Arthrogryposis (PARART, NCT05673265). Patients who had undergone dual-energy X-ray absorptiometry (DXA) and/or vitamin D testing were included in the analysis. Fifty-one patients (mean age, 32.9 ± 12.6 years) were included; 46 had undergone DXA. Thirty-two (32/51, 62.7%) patients had Amyoplasia, and 19 (19/51, 37.3%) had other types of AMC (18 distal arthrogryposis, 1 Larsen). Six patients (6/42, 14.3%) had a lumbar BMD Z score less than − 2. The mean lumbar spine Z score (− 0.03 ± 1.6) was not significantly lower than the expected BMD Z score in the general population. Nine (9/40, 22.5%) and 10 (10/40, 25.0%) patients had femoral neck and total hip BMD Z scores less than − 2, respectively. The mean femoral neck (− 1.1 ± 1.1) and total hip (− 1.2 ± 1.2) BMD Z scores in patients with AMC were significantly lower than expected in the general population (p < 0.001). Femoral neck BMD correlated with height (rs = 0.39, p = 0.01), age (rs = − 0.315, p = 0.48); total hip BMD correlated with height (rs = 0.331, p = 0.04) and calcium levels (rs = 0.41, p = 0.04). Twenty-five patients (25/51, 49.0%) reported 39 fractures. Thirty-one (31/36, 86.1%) patients had 25-hydroxyvitamin D levels less than 75 nmol/l, and 6 (6/36, 16.7%) had 25-hydroxyvitamin D levels less than 75 nmol/l. Adults with AMC had lower hip BMD than expected for their age, and they more frequently showed vitamin D insufficiency. Screening for low BMD by DXA and adding vitamin D supplementation when vitamin D status is insufficient should be considered in adults with AMC, especially if there is a history of falls or fractures.

Association of dietary carbohydrate and fiber ratio with postmenopausal bone mineral density and prevalence of osteoporosis: A cross-sectional study.

This study aimed to investigate the associations of carbohydrate to dietary fiber ratio with bone mineral density (BMD) and the prevalence of osteoporosis in postmenopausal women. This cross-sectional study retrieved the data of 2829 postmenopausal women from the National Health and Nutrition Examination Survey (NHANES) database. Weighted univariable logistic regression models were used to investigate the correlations of carbohydrate, dietary fiber, or carbohydrate to fiber ratio with osteoporosis. Higher dietary fiber intake was correlated with decreased odds ratio of osteoporosis [odds ratio(OR) = 0.96, 95% confidence interval (CI): 0.93 to 0.99]. The odds ratio of osteoporosis in postmenopausal women was elevated as the increase of carbohydrate to fiber ratio (OR = 1.80, 95%CI: 1.10 to 2.96). Carbohydrate to fiber ratio >17.09 was related to increased odds ratio of osteoporosis (OR = 1.63, 95%CI: 1.04 to 2.56). Compared to the carbohydrate to fiber ratio ≤11.59 group, carbohydrate to fiber ratio >17.09 was associated with decreased total femur BMD (β = -0.015, 95%CI: -0.028 to -0.001) and femur neck BMD (β = -0.020, 95%CI: -0.033 to -0.006) in postmenopausal women. The femur neck BMD in postmenopausal women was decreased with the increase of carbohydrate to fiber ratio (β = -0.015, 95%CI: -0.028 to -0.001). In postmenopausal women, a high carbohydrate/fiber ratio >17.09 is associated with an increased risk of osteoporosis and lower hip BMD and high fiber intake is associated with less osteoporosis and higher hip BMD.

Interaction effects of significant risk factors on low bone mineral density in ankylosing spondylitis.

To analyze individually and interactively critical risk factors, which are closely related to low bone mineral density (BMD) in patient with ankylosing spondylitis (AS). A total of 249 AS patients who visited China-Japan Friendship Hospital were included in this training set. Patients with questionnaire data, blood samples, X-rays, and BMD were collected. Logistic regression analysis was employed to identify key risk factors for low BMD in different sites, and predictive accuracy was improved by incorporating the selected significant risk factors into the baseline model, which was then validated using a validation set. The interaction between risk factors was analyzed, and predictive nomograms for low BMD in different sites were established. There were 113 patients with normal BMD, and 136 patients with low BMD. AS patients with hip involvement are more likely to have low BMD in the total hip, whereas those without hip involvement are more prone to low BMD in the lumbar spine. Chest expansion, mSASSS, radiographic average grade of the sacroiliac joint, and hip involvement were significantly associated with low BMD of the femoral neck and total hip. Syndesmophytes, hip involvement and higher radiographic average grade of the sacroiliac joint increases the risk of low BMD of the femoral neck and total hip in an additive manner. Finally, a prediction model was constructed to predict the risk of low BMD in total hip and femoral neck. This study identified hip involvement was strongly associated with low BMD of the total hip in AS patients. Furthermore, the risk of low BMD of the femoral neck and total hip was found to increase in an additive manner with the presence of syndesmophytes, hip involvement, and severe sacroiliitis. This finding may help rheumatologists to identify AS patients who are at a high risk of developing low BMD and prompt early intervention to prevent fractures.

Lrp5 p.Val667Met Variant Compromises Bone Mineral Density and Matrix Properties in Osteoporosis.

Early-onset osteoporosis (EOOP) has been associated with several genes, including LRP5, coding for a coreceptor in the Wnt pathway. Variants in LRP5 were also described in osteoporosis pseudoglioma syndrome, combining severe osteoporosis and eye abnormalities. Genomewide-association studies (GWAS) showed that LRP5 p.Val667Met (V667M) variant is associated with low bone mineral density (BMD) and increased fractures. However, despite association with a bone phenotype in humans and knockout mice, the impact of the variant in bone and eye remains to be investigated. Here, we aimed to evaluate the bone and ocular impact of the V667M variant. We recruited 11 patients carrying the V667M variant or other loss-of-function variants of LRP5 and generated an Lrp5 V667M mutated mice. Patients had low lumbar and hip BMD Z-score and altered bone microarchitecture evaluated by HR-pQCT compared with an age-matched reference population. Murine primary osteoblasts from Lrp5 V667M mice showed lower differentiation capacity, alkaline phosphatase activity, and mineralization capacity in vitro. Ex vivo, mRNA expression of Osx, Col1, and osteocalcin was lower in Lrp5 V667M bones than controls (all p < 0.01). Lrp5 V667M 3-month-old mice, compared with control (CTL) mice, had decreased BMD at the femur (p < 0.01) and lumbar spine (p < 0.01) with normal microarchitecture and bone biomarkers. However, Lrp5 V667M mice revealed a trend toward a lower femoral and vertebral stiffness (p = 0.14) and had a lower hydroxyproline/proline ratio compared with CTL, (p = 0.01), showing altered composition and quality of the bone matrix. Finally, higher tortuosity of retinal vessels was found in the Lrp5 V667M mice and unspecific vascular tortuosity in two patients only. In conclusion, Lrp5 V667M variant is associated with low BMD and impaired bone matrix quality. Retinal vascularization abnormalities were observed in mice. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

The Function of Body Mass Index in the Older with Osteosarcopenia: A Systematic Review and Meta-analysis.

Due to the aging population worldwide, diseases that frequently attack elderly people, such as sarcopenia and osteoporosis, are major public health issues. This study used a systematic review and meta-analysis to examine the associations among body mass index (BMI), sarcopenia, and bone mineral density (BMD) in a group of adults older than 60 years. Eight studies with a total of 18,783 subjects were examined using a random effect model. In sarcopenia patients, total hip BMD (d=0.560; 95% confidence interval [CI], 0.438 to 0.681; P<0.01; I2=53.755%), femoral neck BMD (d=0.522; 95% CI, 0.423 to 0.621; P<0.01; I2=77.736%) and lumbar spine BMD (d=0.295; 95% CI, 0.111 to 0.478; P<0.01; I2=66.174%) were lower than in control subjects. Additionally, BMI (d=0.711; 95% CI, 0.456 to 0.996; P<0.01; I2=97.609%) correlated with the BMD of the total hip, femoral neck, and lumbar spine. That is, sarcopenia patients with low BMD levels in the total hip, femoral neck, and lumbar spine also had low fat levels. Thus, sarcopenia patients with low BMD in the total hip, femoral neck and lumbar spine and low BMI could have a higher than average risk of osteosarcopenia. No sex effects were significant (P>0.05) for any variable. BMI could be a key point in osteosarcopenia, suggesting that a low body weight could be facilitate the transition from sarcopenia to osteosarcopenia.

Risk factors of primary and recurrent fractures in postmenopausal osteoporotic Chinese patients: A retrospective analysis study

BackgroundAs postmenopausal osteoporotic fractures can cause higher rates of disability and mortality in women; it is essential to analyze the factors associated with primary and recurrent fractures in postmenopausal osteoporosis (PMOP) patients.MethodsRetrospective analysis of 2478 PMOP patients aged ≥ 50 years who attended the Shanghai General Hospital from January 2007 to December 2016, including 1239 patients with no fractures and 1239 patients with histories of fractures (1008 in the primary fracture group and 231 in the re-fracture group). All patients' basic clinical data, serum biochemical and bone metabolic markers, bone mineral density (BMD), and other indicators were recorded uniformly. Comparing the differences between the clinical characteristics of patients with primary and recurrent fractures, as well as the differences in the clinical characteristics of patients with primary and recurrent fractures in combination with different diseases, further analyses the risk factors for primary and recurrent fractures in PMOP patients. SPSS.26 was used for statistical analysis.ResultsCompared to the unfractured group, the fractured group was older and had lower height and bone mineral density (all P < 0.01), with the re-fractured group having lower BMD at each key site than the primary fracture group (all P < 0.01). Analysis of the combined disease subgroups showed that serum BGP levels were lower in the primary and re-fracture patients with diabetes than in the non-diabetic subgroup (P < 0.05), and serum CTX levels were lower in the re-fracture group with diabetes than in the primary fracture group with diabetes (P < 0.05). Patients with recurrent fractures with cardio-vascular diseases had lower BMD than the subgroup without cardio-vascular diseases (P < 0.05) and also had lower BMD than the group with primary fractures with cardio-vascular diseases (P < 0.05). Multiple logistic regression analysis showed that advanced age, overweight, low lumbar spine and total hip BMD were risk factors for primary and recurrent fractures; and comorbid chronic liver and kidney diseases were risk factors for primary fractures.ConclusionPMOP patients with advanced age, overweight, low bone mineral density, and comorbid chronic liver and kidney diseases are at greater risk of fractures and require early intervention to reduce fractures occurrence. Moreover, those who are elderly, overweight, and have low bone density should also be aware of the risk of re-fractures.

The association between peripheral arterial disease and risk for hip fractures in elderly men is not explained by low hip bone mineral density. Results from the MrOS Sweden study

SummaryIn this prospective study in Swedish elderly men, PAD based on an ABI < 0.9 was associated with an increased risk of hip fracture, independent of age and hip BMD. However, after further adjustments for comorbidity, medications, physical function, and socioeconomic factors, the association diminished and was no longer statistically significant.IntroductionTo examine if peripheral arterial disease (PAD) is associated with an increased risk for hip fracture in men independent of hip BMD.MethodsAnkle-brachial index (ABI) was assessed in the Swedish MrOS (Osteoporotic Fractures in Men) study, a prospective observational study including 3014 men aged 69–81 years at baseline. PAD was defined as ABI < 0.90. Incident fractures were assessed in computerized X-ray archives. The risk for hip fractures was calculated using Cox proportional hazard models. At baseline, BMD was assessed using DXA (Lunar Prodigy and Hologic QDR 4500) and functional measurements and blood samples were collected. Standardized questionnaires were used to collect information about medical history, falls, and medication.ResultsDuring 10 years of follow-up, 186 men had an incident hip fracture. The hazard ratio (HR) for hip fracture in men with PAD was 1.70 (95% CI 1.14–2.54), adjusted for age and study site. Additional adjustment for total hip BMD marginally affected this association (HR 1.64; 95% CI 1.10–2.45). In a final multivariate model, the HR attenuated to a non-significant HR 1.38 (95% CI 0.91–2.11) adjusted for age, site, hip BMD, BMI, falls, smoking, eGFR, handgrip strength, walking speed, former hip fracture, antihypertensive treatment, diabetes, education, and history of cardiovascular disease.ConclusionThis study suggests that PAD is associated with an increased risk for hip fracture independently of hip BMD in elderly Swedish men. However, the high frequency of comorbidity and lower physical performance among men with PAD might partly explain this association.

Low Dose Daily Prunes Preserve Hip Bone Mineral Density With No Impact on Body Composition in a 12-Month Randomized Controlled Trial in Postmenopausal Women: The Prune Study

ObjectivesDietary consumption of prunes has favorable impacts on bone health, however, more research is necessary to improve upon study designs and refine our understandings and determine whether unfavorable fat gain occurs with long-term treatment. Objectives: Evaluate the effects of prunes (50g and 100g/day) on bone mineral density (BMD) in postmenopausal women during a 12-month dietary intervention. Secondary outcomes include effects on body composition. MethodsSingle center, parallel arm 12-month randomized controlled trial (RCT; NCT02822378) to test effects of 50g and 100g/day prunes vs. a Control group on BMD (dual-energy X-ray absorptiometry) (every 6 months) and body composition in postmenopausal women with a BMD T-score of < 0.0 and >–3.0 at any site. Results235 women (age 62.1 ± 5.0 yr) were randomized into Control (n = 78), 50 g Prune (n = 79), or 100 g Prune (n = 78) groups. Compliance was 90.2 ± 1.8% and 87.1 ± 2.1% in the 50 g and 100 g Prune groups. Dropout was 22%; however, the dropout rate was 41% for the 100 g Prune group compared to other groups (10% Control; 15% 50 g Prune; (p < 0.001)). A group × time interaction for total hip BMD was observed in Control vs 50 g Prune groups (p = 0.030), but not in Control vs 100 g Prune groups (p = 0.194). Prune consumption did not affect body mass in 50 g prune (p = 0.837) or 100 g prune (p = 0.121) groups compared to Control. A group × time interaction for fat mass was observed in Control vs 100 g Prune groups (p = 0.031), but not in Control vs 50 g Prune groups (p = 0.792). ConclusionsA 50 g dose of daily dose of prunes can prevent loss of total hip BMD in postmenopausal women, without increased fat mass seen with the larger dose. Given that there was high compliance and retention at the 50 g dosage over 12 months, we propose that the 50 g dose represents a valuable non-pharmacological treatment strategy that can be used to preserve hip BMD in postmenopausal women, without increasing body or fat mass. Funding SourcesCalifornia Prune Board

Bisphosphonate Drug Holidays: Evidence From Clinical Trials and Real-World Studies.

ABSTRACTBisphosphonates (BPs) are commonly used in the treatment of osteoporosis and are effective in the prevention of fragility fracture. Long‐term use has been associated with the development of atypical femur fractures (AFFs) and osteonecrosis of the jaw (ONJ). Drug holidays seek to reduce the risk of insufficiency fractures (AFFs) while maintaining durable effects of long‐term treatment in the prevention of fragility fracture. Guidelines suggest that BP drug holidays be considered after 3 to 5 years. However individual factors impacting this decision and outcomes are unclear. This review examines key factors in the planning of a safe BP drug holiday and surrogate markers of fracture risk in patients discontinuing treatment. Fifteen randomized control trials and 19 real‐world studies were included, including nationwide prospective studies from several countries. Increases in bone turnover markers (BTMs) and reductions in bone mineral density (BMD) were generally observed during BP drug holidays. Resurgent bone turnover was problematic in high‐risk patients in whom fractures recurred as early as 12 months following a drug holiday. Risk factors for holiday‐related fractures included older age, low hip BMD, underweight, low medication adherence, and prevalent/incident fractures. Zoledronic acid conferred the most durable reduction in fractures, particularly after six annual infusions. Five years of alendronate was insufficient in preventing vertebral fractures in high‐risk patients embarking on a drug holiday. Relatively faster offset of antiresorptive effect was seen in risedronate users with more frequent fractures than alendronate during a drug holiday. Studies directly counterbalancing effects of long‐term treatment on AFF risk versus drug holiday outcomes in the same population were lacking. In the absence of persistently high fracture risk and following a specific treatment duration dependent on the BP used, drug holidays are safe and mitigate the risk of AFF. However, anti‐resorptive effects diminish over time; ongoing monitoring and careful planning of BP resumption is necessary. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Different roles of the RAAS affect bone metabolism in patients with primary aldosteronism, Gitelman syndrome and Bartter syndrome

BackgroundComponents of the RAAS may influence bone metabolism. Different roles of the RAAS are found in patients with primary aldosteronism (PA), Gitelman syndrome (GS) and Bartter syndrome (BS). We collected inpatient medical records including 20 patients with Gitelman syndrome (GS group),17 patients with Bartter syndrome (BS group) and 20 age-matched patients with primary aldosteronism (PA group). We found the following results. (1) PA patients had significantly higher serum magnesium, potassium, plasma aldosterone, serum parathyroid hormone, urinary calcium and BMI (p<0.05) while significantly lower serum calcium and phosphorus (P < 0.05) than GS and BS patients. (2) Total hip and femoral neck bone mineral density (BMD) in PA patients were significantly lower than those in GS and BS patients (P<0.05). (3) GS patients had lower serum magnesium and urinary calcium than BS patients (P < 0.05). (4) Compared with BS patients, the vertebral BMD in GS patients were significantly higher (P < 0.05). So we believe higher aldosterone and PTH levels may be the reason that PA patients have lower hip BMD. Lower urinary calcium and inactivation of the NCC gene (Na-Cl cotransporter) in GS patients may have protective effects on vertebral bone mineral density.ConclusionsWith persistence disordered RAAS, PA patients have lower BMD, especially hip BMD as compared with GS and BS patients. We presumed the lower renin and higher aldosterone level may be the reason. With the same level of renin and aldosterone, BS patients have lower vertebrate BMD than GS patients. Decreased urinary calcium excretion may be the reason.

Screening of Important Markers in Peripheral Blood Mononuclear Cells to Predict Female Osteoporosis Risk Using LASSO Regression Algorithm and SVM Method.

Background:Osteoporosis is a bone disease that increases the patient’s risk of fracture. We aimed to identify robust marker genes related to osteoporosis based on different bioinformatic methods and multiple datasets.Methods:Three datasets from Gene Expression Omnibus (GEO) were utilized for analysis separately. Significantly differentially expressed genes (DEGs) from comparing high hip and low hip low bone mineral density (BMD) groups in the first dataset were identified for Gene Ontology (GO), Gene set enrichment analysis (GSEA) and Kyoto encyclopedia of genes and genomes (KEGG) to investigate the discrepantly enriched biological processes between high hip and low hip group. Last absolute shrinkage and selection operator (LASSO), SVM model and protein-protein interaction (PPI) regulatory network were performed and generated robust marker genes for downstream TF-target and miRNA-target prediction.Results:Several DEGs between high hip BMD group and low hip BMD group were obtained. And the metabolism-related pathways such as metabolic pathways, carbon metabolism, glyoxylate and dicarboxylate metabolism shown enrichment in these DEGs. Integration with LASSO regression analysis, 8 differential expression genes (SH3BP1, NARF, ANKRD34B, RNF40, ZNF473, AKT1, SHMT1, and VASH1) in GSE62402 were identified as the optimal differential genes combination. Moreover, the SVM validation analysis in GSE56814 and GSE56815 datasets showed that the characteristic gene combinations presented high diagnostic effects, and the model AUC areas for GSE56814 was 0.899 and for GSE56815 was 0.921. Furthermore, the subcellular localization analysis of the 8 genes revealed that 4 proteins were located in the cytoplasm, 3 proteins were located in the nucleus, and 1 protein was located in the mitochondria. Additionally, the related TFs and miRNAs by performing TF-target and miRNA-target prediction for 5 genes (AKT1, SHMT1, ZNF473, RNF40 and VASH1) were investigated from PPI network.Conclusion:The optimal differential genes combination (SH3BP1, NARF, ANKRD34B, RNF40, ZNF473, AKT1, SHMT1, and VASH1) presented high diagnostic effect for osteoporosis risk.

Assessment of Serum sRANKL, sRANKL/OPG Ratio, and Other Bone Turnover Markers with the Estimated 10-Year Risk of Major and Hip Osteoporotic Fractures in Rheumatoid Arthritis: A Cross-Sectional Study.

Background Fracture risk assessment tool (FRAX) index was developed for estimating of the 10-year risk of major or hip osteoporotic fracture. To date, there is insufficient information regarding the correlation between FRAX and serum bone turnover markers (BTMs), such as soluble ligand of receptor activator of nuclear factor-κB (sRANKL), osteoprotegerin (OPG), and other molecules related with secondary osteoporosis in rheumatoid arthritis (RA). Therefore, this study is aimed at assessing the correlation between the FRAX and serum levels of sRANKL, OPG, sRANKL/OPG ratio, Dickkopf-1 (DKK-1), and sclerostin (SOST) in RA. Methods Cross-sectional study included 156 postmenopausal women with RA. Bone mineral density (BMD) was measured at lumbar spine (L1-L4) and total hip using dual-energy X-ray absorptiometry (DXA). RA patients were divided into (A) RA + osteoporosis and (B) RA without osteoporosis. FRAX scores were calculated including the total hip BMD. Serum sRANKL, OPG, DKK-1, and SOST levels were measured by ELISA. Pearson tests were used for assessing the correlation between serum levels of these molecules and FRAX scores in RA. Results The RA + osteoporosis group had elevated sRANKL levels (p = 0.005), higher sRANKL/OPG ratio (p = 0.017), decreased DKK-1 (p = 0.028), and lower SOST levels (p < 0.001). Low total hip BMD correlated with high sRANKL (p = 0.001) and sRANKL/OPG ratio (p = 0.005). Total hip and lumbar spine BMD correlated with DKK-1 (p = 0.009 and p = 0.05, respectively) and SOST levels (p < 0.001 and p < 0.001, respectively). Higher sRANKL levels and sRANKL/OPG ratio correlated with estimated 10-year risk of a major osteoporotic fractures (p = 0.003 and p = 0.003, respectively) and hip fracture (p = 0.002 and p = 0.006, respectively). High serum SOST levels were associated with a low estimated 10-year risk of a major osteoporotic fracture (p = 0.003) and hip fracture (p = 0.009). Conclusion High sRANKL levels and sRANKL/OPG ratio can be useful to detect a subgroup of RA patients who has an increased 10-year risk of major and hip osteoporotic fractures.

The association between bone mineral density and postoperative drainage volume following cruciate-substituting primary total knee arthroplasty: a cross-sectional study

BackgroundThe prevalence of osteoporosis in patients who undergo a primary total knee arthroplasty (TKA) is increasing. Low bone mineral density (BMD) is related to unfavorable outcomes following TKA such as migration of uncemented tibial components. Postoperative blood loss in TKA is an important complication. Non-modifying predicting factors for postoperative blood loss in patients undergoing primary TKA need further elucidation. Studies on the association between BMD and blood loss after TKA are limited. We aimed to demonstrate the relationship between BMD and postoperative drainage volume following primary TKA.MethodsA cross-sectional study was conducted between January 2014 and August 2020. A total of 119 primary varus osteoarthritis knees with BMD results were included in the study. Patients with secondary causes of osteoporosis were excluded.ResultsThe median postoperative drainage volume of participants in the normal total hip BMD group and the normal trochanter BMD group was higher than that of patients in the low total hip BMD group and the low trochanter BMD group (285.0 ml vs 230.0 ml, P = 0.003; 282.5 ml vs 240.0 ml, P = 0.013, respectively). Multivariate regression analyses showed that operative time, spinal anesthesia, and normal total hip BMD status were significant predictive factors associated with increased postoperative drainage volume (P = 0.014, 0.022, and 0.013, respectively). No association was identified between the lumbar spine BMD status and postoperative drainage volume.ConclusionsThe relationship between BMD and postoperative blood loss in primary TKA was identified in this study. Normal total hip BMD was found to be associated with an increased postoperative drainage volume after primary TKA compared with low BMD.

Prevalence and Associated Factors of Low Bone Mineral Density in the Femoral Neck and Total Hip in Axial Spondyloarthritis: Data from the CASTRO Cohort

Studies on osteoporosis in axial spondyloarthritis (axSpA) have focused on the lumbar segment, and few studies have assessed bone mineral density (BMD) in the hip and femoral neck in these patients. The aim of this study was to evaluate the prevalence of low BMD and osteopenia in the total hip or femoral neck and the factors associated with these conditions in axSpA patients. This was a single-centre, observational, cross-sectional study among consecutive patients with axSpA according to the ASAS criteria from the CASTRO registry. All patients underwent total hip and femoral neck DXA BMD measurements. Low BMD was defined as a Z-score less than −1, and osteopenia was defined as a T-score less than −1. Multivariate logistic and generalised linear regressions were used to evaluate factors independently associated with low BMD and osteopenia in the hip or femoral neck and those associated with variability in BMD, respectively. A total of 117 patients were included, among which 30.8% were female and the mean age was 45 years. A total of 36.0% of patients had low BMD (28.1% in the total hip and 27.4% in the femoral neck), and 56.0% of patients had osteopenia (44.7% in the total hip and 53.8% in the femoral neck). A multivariate logistic regression showed that age, radiographic sacroiliitis and ASAS-HI were independently associated with low BMD in the total hip or femoral neck. Factors that were independently associated with osteopenia were Body Mass Index, disease duration, radiographic sacroiliitis and ASAS-HI. In conclusion, 36% of the patients with axSpA had low BMD in the total hip or femoral neck. A younger age and radiographic sacroiliitis were the most important factors associated with decreased BMD.

Bone mineral density in Canadian children with severe haemophilia A or B: a cross-sectional study

Abstract Background Previous research has shown that bone mineral density (BMD), a measure of bone strength, may be lower among people with haemophilia. However, the majority of this research has been done in adults and in countries where the treatment for haemophilia differs from the standard of care in Canada, and there is a lack of paediatric data. Aims The primary objective of this study was to determine whether Canadian children and youth with severe haemophilia A and B have BMD similar to healthy controls matched for height, age and weight (HAW-score). Secondary objectives included the exploration of any association between BMD and the following variables: factor replacement regimen, Hemophilia Joint Health Score (HJHS), bleeding history, physical activity level, and dietary intake of calcium, vitamin D, vitamin K and protein. Methods A cross-sectional observational study was designed to determine the BMD of children with severe haemophilia A and B in Canada. Ethical approvals were obtained from participating institutions. Thirty-eight participants aged 3–18 with severe haemophilia A and B were recruited from two treatment centres in Canada. Subjects underwent dual-energy X-ray absorptiometry (DXA) scan, and data was collected from regular clinic visit to identify factor replacement regimen, HJHS, and number of joint bleeds over the lifespan. Physical activity level and dietary intake of calcium, vitamin D, vitamin K and protein were identified using self-report questionnaires. Results Participants showed a mean spine BMD Z-score and HAW-score higher than controls, with no participants showing a spine Z-score or HAW-score of &lt;0. Hip BMD score was within normal range, and 2 participants had a Z-score and HAW-score of &lt;−2. Total body BMD score was lower than controls, with 6 participants having a Z-score of &lt;−2.0, and 3 participants having a HAW-score of &lt;−2.0. Factor replacement regimen, HJHS, calcium intake, and physical activity level had no relationship to BMD Z-score or HAW-score. Low intake of vitamin D was associated with a low hip and spine BMD Z-score and HAW-score. Participants with a HJHS joint score greater than 0 had a higher total body HAW-score than those who had a joint score of 0. Conclusion Canadian children with severe haemophilia A and B demonstrate differences in spine and total body BMD from height-, age-, and weight-matched controls, where spine BMD is higher than controls and total body BMD is lower than controls. Studies with a larger sample size are needed to clarify the status of BMD in children with haemophilia treated with primary prophylaxis.

Personality Disorder and Physical Health Comorbidities: A Link With Bone Health?

We examined whether personality disorders (PDs) (any, cluster A/B/C) were associated with bone mineral density (BMD) in a population-based sample of Australian women (n = 696). Personality and mood disorders were assessed using semi-structured diagnostic interviews. BMD was measured at the spine, hip, and total body using dual-energy x-ray absorptiometry (GE-Lunar Prodigy). Anthropometrics, medication use, physical conditions, and lifestyle factors were documented. The association between PDs (any, cluster A/B/C) and BMD (spine/hip/total body) was examined with multiple linear regression models. The best models were identified by backward elimination including age, weight, physical activity, smoking status, alcohol consumption, dietary calcium intake, mood disorders, physical multimorbidity, socioeconomic status, and medications affecting bone. The variables were retained in the model if p < 0.05. All potential interactions in final models were tested. Those with cluster A PD, compared to those without, had 6.7% lower hip BMD [age, weight adjusted mean 0.853 (95% CI 0.803–0.903) vs. 0.910 (95% CI 0.901–0.919) g/cm2, p = 0.027] and 3.4% lower total body BMD [age, weight, smoking, alcohol, calcium adjusted mean 1.102 (95% CI 1.064–1.140) vs. 1.139 (95% CI 1.128–1.150) g/cm2, p = 0.056]. No associations were observed between cluster B/C PDs and hip/total body BMD or between any of the PD clusters and spine BMD. To our knowledge, this study is the first to investigate the bone health of women with PD in a population-based sample. Given the paucity of literature, replication and longitudinal research including the examination of underlying mechanisms and sex differences are warranted.

Fractures After Denosumab Discontinuation: A Retrospective Study of 797 Cases.

ABSTRACTA rebound of osteoclast activity during the 2 years after a treatment or prevention of osteoporosis with denosumab (Dmab) leads to an increased risk of vertebral fractures (VFs). We attempted to identify the risk factors for these VF and to examine the protective role of bisphosphonates. For that, 22 specialists in Switzerland provided data of unselected patients, treated with denosumab for osteoporosis or breast cancer without metastases under aromatase inhibitors, who have received at least two injections of Dmab, with at least 1 year of follow‐up after discontinuation. The questionnaire covered separately the periods before, during, and after Dmab treatment, and registered clinical, radiological, and lab data. For the analysis of the risk factors, the main outcomes were the time to the first VF after the treatment, the presence of multiple VFs (MVFs), and the number of VFs. The incidence of VF was 16.4% before, 2.2% during, and 10.3% after the treatment with Dmab. The risk of VF after Dmab discontinuation was associated with an increased risk of non‐vertebral fractures. The pretreatment predictors of the post‐treatment fracture risk were a parental hip fracture and previous VFs. Further risk factors appeared later, such as low total hip bone mineral density (BMD) during and after denosumab, increased bone resorption markers, and the loss of total hip BMD after the denosumab. Treatment with bisphosphonates, especially after Dmab, had a protective effect. Bisphosphonates given before Dmab did not further decrease the risk of VF in cases who got bisphosphonates after Dmab. This study shows that the risk of VF is poorly predictable before the prescription of denosumab. But during and after the treatment, bone resorption markers and BMD have a significant predictive value. Bisphosphonates after the treatment with denosumab are protective against VFs. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Associations Between Tenofovir Diphosphate in Dried Blood Spots, Impaired Physical Function, and Fracture Risk.

BackgroundIn this study, we evaluate associations between cumulative antiretroviral adherence/exposure, quantified using tenofovir diphosphate (TFV-DP) in dried blood spots (DBS), and human immunodeficiency virus (HIV)-related aging factors. MethodsThis is a cross-sectional analysis of younger (ages 18–35) and older (ages ≥60) persons with HIV (PWH) taking TFV disoproxil fumarate. Tenofovir diphosphate concentrations were quantified in DBS. Linear and logistic regression models were used to evaluate associations between TFV-DP and bone mineral density (BMD), physical function, frailty, and falls.ResultsForty-five PWH were enrolled (23 younger, 22 older). Every 500 fmol/punch (equivalent to an increase in ~2 doses/week) increase in TFV-DP was associated with decreased hip BMD (−0.021 g/cm2; 95% confidence interval [CI], −0.040 to −0.002; P = .03). Adjusting for total fat mass, every 500 fmol/punch increase in TFV-DP was associated with higher odds of Short Physical Performance Battery impairment (score ≤10; adjusted odds ratio [OR], 1.6; 95% CI, 1.0–2.5; P = .04). Every 500 fmol/punch increase in TFV-DP was associated with slower 400-meter walk time (14.8 seconds; 95% CI, 3.8–25.8; P = .01) and remained significant after adjusting for age, lean body mass, body mass index (BMI), and fat mass (all P ≤ .01). Every 500 fmol/punch increase in TFV-DP was associated with higher odds of reporting a fall in the prior 6 months (OR, 1.8; 95% CI, 1.1–2.8; P = .02); this remained significant after adjusting for age, lean body mass, BMI, and total fat mass (all P < .05).ConclusionsHigher TFV-DP levels were associated with lower hip BMD, poorer physical function, and greater risk for falls, a concerning combination for increased fracture risk.

Factors Associated With Kyphosis and Kyphosis Progression in Older Men: The MrOS Study.

Hyperkyphosis (HK), or increased anterior curvature of the thoracic spine, is common in older persons. Although it is thought that vertebral fractures are the major cause of HK, only about a third of those with the worst degrees of kyphosis have underlying vertebral fractures. In older men, HK is associated with increased risk of poor physical function, injurious falls, and earlier mortality, but its causes are not well understood. We studied 1092 men from the Osteoporotic Fractures in Men (MrOS) Study aged 64 to 92 years (mean age 72.8 years) who had repeated standardized radiographic measures of Cobb angle of kyphosis to identify risk factors for HK (defined as ≥50 degrees) and kyphosis progression over an interval of 4.7 years. Specifically, we examined the associations with age, body mass index (BMI), weight, weight loss, health behaviors, family history of HK, muscle strength, degenerative disc disease (DDD), bone mineral density (BMD), prevalent thoracic vertebral fractures, and incident thoracic vertebral fractures (longitudinal analyses only). Men had an average baseline kyphosis of 38.9 (standard deviation [SD] 11.4) degrees. Fifteen percent had HK (n = 161) with a mean Cobb angle of 56.7 (SD = 6.0) degrees; these men were older (p < 0.01), had lower BMI (p < 0.01), lower BMD (p < 0.01), were more likely to have family history of HK (p = 0.01), and prevalent thoracic vertebral fracture (p < 0.01) compared with the men without HK. During follow-up, men experienced an average of 1.4 degrees of kyphosis progression with DDD (p = 0.04) and lower hip BMD (p < 0.01) being identified as statistically significant and incident vertebral fractures (p = 0.05) nearly significant factors associated with worse progression. These results suggest that in older men, HK results from not only low BMD and vertebral fractures but that DDD also may play a significant role in kyphosis progression. © 2020 American Society for Bone and Mineral Research (ASBMR).