Altered Bone Mineral Density Research Articles

P0324 Lower Bone Mineral Density and alterations in bone biomarkers DKK-1, Sclerostin, and Periostin in individuals with Inflammatory Bowel Disease

Abstract Background Inflammatory Bowel Disease (IBD) affects the gastrointestinal tract but often presents with extraintestinal manifestations in many patients, including the decline in bone mass. The pathogenesis of IBD is primarily attributed to disturbances in immune responses within the gastrointestinal mucosa and potential disruptions in gut microbiomes. The inflammation of gastrointestinal tract triggers various systems, including the Wnt pathway, which is associated with bone loss. This study explores the alterations in Bone Mineral Density (BMD) and the levels of dickkopf-1(DKK-1), sclerostin (SOST), periostin (POSTN) and bone metabolism markers in IBD patients. Methods We evaluated a cohort of 89 individuals diagnosed with IBD (64% male, 65% with Crohn’s disease, and 35% with ulcerative colitis) with a median (interquartile range) age of 39(28, 54) years and 73 controls of 42(29, 54) years. Bone Mineral Density (BMD) was evaluated using dual-energy x-ray absorptiometry (DXA). We also measured DKK-1, SOST, POSTN, biochemical parameters and bone metabolism markers in the plasma and serum of participants. Results Femoral neck BMD Z-score was lower -0.7(-1.65, 0.2) vs -0.3(-1.1, 0.2) SD, p=0.04, while there was a trend for lower lumbar spine BMD Z-score in patients. Increased C-terminal telopeptides (CTX) 0.49(0.28, 0.68) vs 0.34(0.24, 0.47) pg/mL, p<0.001 and N-terminal telopeptides (NTX) levels 17(13, 23) vs 13.5(11, 18) nMBCE, p<0.001 were observed in patient group, while procollagen-1 N-propeptide and osteocalcin levels had comparable levels. Phosphorus and 25(OH)D levels were comparable between groups, while calcium levels were higher in patients 9.4(9, 9.7) vs 8.9(8.7, 9.2) mg/dl, p=0.02. Parathyroid hormone (PTH) 42(33, 54) vs 51(37, 63) pg/mL, p=0.009 as well as magnesium levels 2(1.8, 2.1) vs 2.1 (2, 2.2), p=0.02 were lower in the patient group. IBD patients exhibited elevated DKK1 levels 2359 (2104, 2583) vs 1580(1419, 1733) pg/mL, p<0.001 and reduced sclerostin 375(313, 501) vs 724(570, 899) pg/mL, p<0.001 and periostin levels 150(108, 204) vs 217(181, 312) ng/mL, p<0.001. DKK1 levels were positively correlated with CTX rho=0.27, p<0.001 and NTX rho=0.26, p<0.001 and negatively correlated with lumbar BMD Z-score rho=-0.21, p=0.02. Conclusion IBD patients were found with an osteopenic phenotype, which can be the consequence of bone loss due to osteoblast activation and increased bone resorption as indicated by increased CTX and NTX levels and osteoblast and osteocyte suppression as indicated by higher DKK-1 and lower periostin and sclerostin levels. The inflammation itself, malabsorption of nutrients, medications (e.g. corticosteroids), and low energy intake could contribute to those pathophysiological changes.

Subchondral Bone Degeneration and Pathology 3-15 Years Following Ankle Sprain Injury in Adolescent Sport.

Sport-related ankle sprains (SASs) are prevalent in adolescents (ages 10-19), increasing the risk of developing posttraumatic osteoarthritis (PTOA). Although early ankle osteoarthritis (OA) is not well defined, OA eventually includes alterations in bone mineral density (BMD), structural changes, and soft tissue pathology. This study examined the impact of SAS sustained in adolescent sport on bone and soft tissue structural outcomes 3-15 years postinjury. Participants (n = 10) with prior unilateral SAS in adolescent sport (HxAI) were compared to age- and sex-matched controls. To assess injury-related pathologies and BMD, 1.5-tesla (T) extremity magnetic resonance imaging (MRI) and computed tomography scans were used. Semiquantitative scores for injury patterns and OA features from MRI scans were summed and compared between groups. The talus, calcaneus, navicular, and 5% distal tibia were segmented, and BMD was measured for each bone. All HxAI participants exhibited MRI injury pathology (median 2; IQR 1-6), whereas only 1 of 10 controls showed pathology (median 0; IQR 0-0), χ2(1, n = 20) = 16.36, P < .001. Both the injured and uninjured ankles in HxAI displayed injury pattern pathology. Additionally, 3 of 10 injured ankles and 2 of 10 uninjured ankles in the HxAI group (median 0; IQR 0-3), but none of the controls (median 0; IQR 0-0), exhibited OA features. In the HxAI group, talus BMD was lower in the injured ankle (502.4 ± 67.9 g/cm3) compared with the uninjured ankle (515.6 ± 70.1 g/cm3) (F = 13.33, P = .002), with no significant BMD differences at the calcaneus, navicular, or 5% distal tibia. No differences were observed between the ankles of the control group. The presence of injury pattern pathology, structural changes, and reduced talus BMD suggest that degenerative changes may occur in individuals as early as 3-15 years following ankle injury.

Роль окислительного стресса в патогенезе остеодеструктивного синдрома у больных с хроническим лимфолейкозом

Reduced bone mineral density (BMD), osteopenia, and osteoporosis are slightly more common in patients with chronic lymphocytic leukemia (CLL). The risk of osteoporotic fractures in individuals with CLL is higher, than in healthy individuals of the same age. The mechanism underlying the CLL-associated BMD reduction can be related to decreased antioxidant protection and oxidative stress (OS). The study aimed to assess the relationship between oxidative stress, antioxidant protection, and osteopenia indicators in patients with CLL. Males aged 50–70 years were examined. Group 1 consisted of 14 healthy men, group 2 consisted of 54 patients with CLL having no BMD alterations, and group 3 consisted of 22 patients with CLL having signs of osteopenia. A densitometer was used to estimate BMD, T- and Z-scores of the lumbar vertebrae, proximal femoral neck (PFN), proximal femoral bone in all groups. At the beginning of the study, the levels of lipid peroxidation (LPO) products were determined in blood serum in all groups and bone tissue homogenate in groups 2 and 3; the total antioxidant status (TAS) was also determined. Bone densitometry indicators, serum LPO and TAS were assessed in all groups after 6 months of follow-up. At the beginning of the study osteopenia in PFN based on bone densitometry data was revealed in 29% of patients, while 6 months later osteopenia of all localizations was observed in 55% of patients. At the beginning of the study patients with CLL and osteopenia showed OS and reduced TAS in both blood serum and bone tissue. After 6 months patients with CLL and osteopenia showed signs of OS progression and TAS reduction. In patients with CLL, serum and bone tissue OS indicators are comparable and can be used to predict the onset of osteopenia within 6 months.

Impact of Different Anti-Hyperglycaemic Treatments on Bone Turnover Markers and Bone Mineral Density in Type 2 Diabetes Mellitus Patients: A Systematic Review and Meta-Analysis.

Diabetic bone disease (DBD) is a frequent complication in patients with type 2 diabetes mellitus (T2DM), characterised by altered bone mineral density (BMD) and bone turnover marker (BTMs) levels. The impact of different anti-diabetic medications on the skeleton remains unclear, and studies have reported conflicting results; thus, the need for a comprehensive systematic review is of paramount importance. A systematic search was conducted in PubMed and the Cochrane Library. The primary outcomes assessed were changes in BMD in relation to different anatomical sites and BTMs, including mainly P1NP and CTX as well as OPG, OCN, B-ALP and RANK-L. Risk of bias was evaluated using the JADAD score. The meta-analysis of 19 randomised controlled trials comprising 4914 patients showed that anti-diabetic medications overall increased BMD at the lumbar spine (SMD: 0.93, 95% CI [0.13, 1.73], p = 0.02), femoral neck (SMD: 1.10, 95% CI [0.47, 1.74], p = 0.0007) and in total hip (SMD: 0.33, 95% CI [-0.25, 0.92], p = 0.27) in comparison with placebo, but when compared with metformin, the overall effect favoured metformin over other treatments (SMD: -0.23, 95% CI [-0.39, -0.07], p = 0.004). GLP-1 receptor agonists and insulin analogues seem to improve BMD compared to placebo, while SGLT2 inhibitors and thiazolidinediones (TZDs) showed no significant effect, although studies' number cannot lead to safe conclusions. For BTMs, TZDs significantly increased P1NP levels compared to placebo. However, no significant differences were observed for CTX, B-ALP, OCN, OPG, and RANK-L between anti-diabetic drugs and metformin or placebo. High heterogeneity and diverse follow-up durations among studies were evident, which obscures the validity of the results. This review highlights the variable effects of anti-diabetic drugs on DBD in T2DM patients, emphasising the need for long-term trials with robust designs to better understand these relationships and inform clinical decisions.

Assessment of the relationship between gut microbiota and bone mineral density: a two-sample Mendelian randomization study.

Emerging evidence from observational studies and clinical trials suggests a connection between the gut microbiota and variations in bone mineral density (BMD). Nonetheless, the specific association between gut microbiota and BMD alterations at different skeletal sites has not been comprehensively explored. To address this, we employed Genome-Wide Association Study (GWAS) summary statistics from a publicly accessible database, conducting a two-sample Mendelian Randomization analysis to elucidate the potential causal relationship between gut microbiota composition and BMD. This study utilized two distinct thresholds for screening instrumental variables (IVs), followed by an extensive series of quality control procedures to identify IVs that were significantly related to exposure. Gut microbiota were classified into two sets based on hierarchical levels: phylum, class, order, family, and genus. Bone mineral density (BMD) data were systematically collected from four skeletal sites: femoral neck, lumbar spine, forearm, and heel. For Mendelian Randomization (MR) analysis, robust methods including Inverse-Variance Weighting (IVW) and the Wald Ratio Test were employed. Additional analytical tests such as the Outlier Test, Heterogeneity Test, 'Leave-One-Out' Test, and Pleiotropy Test were conducted to assess the impact of horizontal pleiotropy, heterogeneities, and the genetic variation stability of gut microbiota on BMD causal associations. The MR Steiger Directionality Test was applied to exclude studies with potential directional biases. In this two-sample Mendelian randomization analysis, we utilized five sets of exposure GWAS (Genome-Wide Association Studies) summary statistics and four sets of outcome GWAS summary statistics. The initial analysis, applying a threshold of p < 5 × 10-6, identified 48 significant causal relationships between genetic liability in the gut microbiome and bone mineral density (BMD). A subsequent analysis with a more stringent threshold of p < 5 × 10-8 uncovered 14 additional causal relationships. Upon applying the Bonferroni correction, 9 results from the first analysis and 10 from the second remained statistically significant. Our MR analysis revealed a causal relationship between gut microbiota and bone mineral density at all sites, which could lead to discoveries in future mechanistic and clinical studies of microbiota-associated osteoporosis.

Bone mineral density changes around the stem correlate with stress changes after total hip arthroplasty: A study using thermoelastic stress analysis.

Thermoelastic stress analysis (TSA) was used to evaluate stress changes over the entire surface of a specimen. This study aimed to assess the relationship between femoral stress distribution, analysed using TSA and changes in bone mineral density (BMD) after total hip arthroplasty (THA). Stress changes in the simulated bone before and after taper-wedge stem insertion were measured using the TSA. Stress changes were compared with BMD changes around the stem 1 year after surgery in a THA patient (58 hips) with the same taper-wedge stem. Subsequently, we compared the correlation between stress changes and BMD changes. TSA revealed significant stress changes before and after stem insertion, with prominent alterations in the proximal medial region. The BMD changes at 1 year post-THA exhibited a 15%-25% decrease in the proximal zones, while Zones 2-6 showed a -6% to 3% change. Notably, a strong positive correlation (0.886) was found between the stress change rate and BMD change rate. This study demonstrated a high correlation between femoral stress distribution assessed using TSA and subsequent BMD changes after THA. The TSA method offers the potential to predict stress distribution and BMD alterations postsurgery, aiding in implant development and clinical assessment. Combining TSA with finite element analysis could provide even more detailed insights into stress distribution. Case series (with or without comparison).

Estrogen deficiency in rats alters the expression and localization of redox proteins in the bone and bone marrow

Imbalances in bone formation/bone resorption ratio can occur under diverse conditions and diseases leading to an alteration of bone mineral density and strength. One of the most dramatic changes altering bone’s microarchitecture occurs under estrogen deficient conditions in humans and in other mammals. For instance, estrogen deficiency during menopause in women induces the formation and accumulation of reactive oxygen species (ROS) and a dysregulation of redox signaling. The bone and bone marrow are especially susceptible to the effects of oxidative stress and ROS. In tissues like the bone, cells are equipped with important defense systems to maintain homeostasis and to survive. Redox proteins of the thioredoxin family represent the most important protective system in cells that act against ROS and repair their intracellular effects. Redox proteins of the thioredoxin family comprise thioredoxins (Trxs), glutaredoxins (Grxs), and peroxiredoxins (Prxs). From all these protein classes, Prxs are the only ones that work as classical ROS scavengers being able to reduce hydrogen peroxide (H2O2), peroxynitrites and organic peroxides. Prxs are localized in different cellular compartments such as mitochondria (Prx3), cytosol and nucleus (Prx1 and Prx2), endoplasmic reticulum (Prx4), and peroxisomes (Prx5). We hypothesized that changes in estrogen levels may alter the expression and localization of Prxs in the bone and bone marrow. In this study, we analyzed the cellular localization and expression patterns of Prxs in the bone and bone marrow of rats as well as the effects of estrogens on their expression levels. We compared sham, ovariectomized, as well as ovariectomized/estrogen-replaced female rats of the same age. Western blot and immunohistochemistry revealed that all peroxiredoxins were abundantly expressed in different cell types of the bone and bone marrow such as osteocytes, chondrocytes, osteoclasts, bone lining cells, osteoblasts, and hematopoietic precursor cells. After ovariectomy, redox protein levels were significantly reduced in most cell types of the bone and bone marrow compartment. In addition to this, estrogen deficient animals showed increased levels of Prx1 in bone marrow supernatant suggesting a major redox dysregulation in this compartment. Estrogen replacement restored the levels of most redox proteins in the bone and bone marrow compartment and reduced the amount of extracellular Prx1. Based on these results, we conclude that estrogen deficiency negatively affects the ability of bone and bone marrow cells to maintain redox proteins at physiological levels. These results also reveal the widespread effects that are mediated by estrogen affecting different protein systems and tissues in the body. This work was funded by a Seed Discovery Grant (grant #3670920201102 to JG) from Long Island University. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The prognostic significance of fibroblast growth factor-23 in predicting complications of type 2 diabetes mellitus, especially when associated with obesity

type 2 Diabetes Mellitus (T2DM) is considered a global health problem with an exceptionally high economic burden not only for families but also for countries overall. In 90-95% of T2DM cases, varying degrees of obesity are observed. One aspect contributing to complications in T2DM involves musculoskeletal system impairment, specifically alterations in bone mineral density (BMD), indicative of bone architecture disruption, leading to secondary osteoporotic conditions. Fibroblast growth factors (FGFs), known for their regulatory influence on metabolism, are identified as mechanisms activated in T2DM. Within this group, fibroblast growth factor 23 (FGF-23) is acknowledged. In individuals with T2DM and excess weight or obesity, conditions conducive to increased FGF-23 synthesis are established, contributing to disturbances in mineral metabolism. Therefore, our study aimed to investigate the content and role of FGF-23 in the development of secondary osteoporosis in T2DM patients with concurrent obesity. A total of 103 patients with type 2 diabetes were involved, with 83 cases featuring elevated body weight or obesity (main group). To assess the impact of obesity on FGF-23 changes, a comparison group of 20 T2DM patients with normal body weight (NBW) was formed. The average age of patients with comorbid conditions was 43±4.6 years, and for those with isolated T2DM, it was 44.1±2.1 years. The average duration of T2DM across groups ranged from 1 to 13 years (6.7±2.4 years on average). Control FGF-23 values were obtained from a group of 20 practically healthy individuals of similar age and gender. The diagnosis of T2DM was confirmed according to the Unified Medical Assistance Protocol "Diabetes Mellitus" (Order of the Ministry of Health of Ukraine dated December 21, 2012, No. 1118). Thus, all examined T2DM patients were in the subcompensation stage with a moderate degree of disease severity. The presence and severity of obesity were assessed according to the International Diabetes Federation (IDF, 2005) criteria based on the body mass index (BMI) calculation using the Ketle formula. In the examination of 83 T2DM patients with obesity, a probable increase in fibroblast growth factor 23 (FGF-23) in serum was determined, correlating with osteoporotic changes in dual-energy X-ray absorptiometry. Therefore, FGF-23 can be utilized as a marker for bone mineral density status and control of treatment measures.

Rat bone responses to hindlimb unloading-reloading: Composition, BMD and mechanical properties

IntroductionBone loss in lower limbs under space microgravity condition can persist even after the astronauts return to Earth's gravitational environment. It is crucial to determine the extent and timing of bone recovery after spaceflight, especially for long-term flights. However, there is a lack of comprehensive descriptions of the recovery of various aspects of bone quality, particularly in terms of compositional characteristics that reflect changes in bone quality. Therefore, the objective of this study is to investigate the alterations in bone mineral density, composition characteristics, and mechanical properties of rat lower limbs during unloading (tail suspension) and the subsequent recovery loading period. MethodsRats were subjected to tail suspension for four weeks (TS4) followed by reloading for an additional four weeks. Bone mineral density (BMD) was measured by μ-CT and analyzed. The mechanical properties of the tibia were assessed by a three-point bending test, and the composition characteristics of bone tissue were evaluated using Raman spectroscopy. Regression analysis was performed to identify main component related to mechanical property. ResultsIn the metaphysis, BMD of the tibia significant decreased, particularly in trabecular bone. Upon reloading, only the cortical bone showed recovery. In the diaphysis, cortical bone remained unchanged during unloading but demonstrated delayed bone loss during the reloading period. Simultaneously, the mechanical properties of tibia experienced a substantial reduction after four weeks of unloading, The stiffness and maximum strength did not fully recover, though the elastic modulus and the ultimate strength were restored following the reloading process. Raman spectroscopy characterization found an increase in the carbonate substitution and crystal crystallinity of the diaphysis after 4 weeks of unloading. There was an intriguing alteration in the mineralized collagen ratio, that an increase was observed in the diaphysis while a decrease was observed in the metaphysis. During 4 weeks of reloading, the compositional characteristics of the diaphysis recovered earlier than those of the metaphysis, with the exception of crystallinity which remained unrecovered. Regression analysis indicated that carbonate replacement has a strong correlation to bone mechanical properties during the 4 weeks of unloading and subsequent 4 weeks of reloading. ConclusionsThe data obtained in this study highlight the incomplete recovery of bone mineral density, mechanical properties, and compositional characteristics during reloading in tail-suspended rats. These findings deepen our understanding of microgravity-induced bone loss and provide valuable information to develop interventions not only for astronauts but also for persons on earth during and after prolonged periods of unloading.

Hyperprolactinemia Due to Prolactinoma has an Adverse Impact on Bone Health with Predominant Impact on Trabecular Bone: A Systematic Review and Meta-Analysis

Background: No meta-analysis has holistically analysed and summarized the effect of prolactin excess due to prolactinomas on bone mineral metabolism. We undertook this meta-analysis to address this knowledge-gap. Methods: Electronic databases were searched for studies having patients with hyperprolactinemia due to prolactinoma and the other being a matched control group. The primary outcome was to evaluate the differences in BMD Z-scores at different sites. The secondary outcomes of this study were to evaluate the alterations in bone mineral density, bone mineral content and the occurrence of fragility fractures. Results: Data from 4 studies involving 437 individuals was analysed to find out the impact of prolactinoma on bone mineral metabolism. Individuals with prolactinoma had significantly lower Z scores at the lumbar spine [MD -1.08 (95 % CI: -1.57 – -0.59); P < 0.0001; I2 = 54 % (moderate heterogeneity)] but not at the femur neck [MD -1.31 (95 % CI: -3.07 – 0.45); P = 0.15; I2 = 98 % (high heterogeneity)] as compared to controls. Trabecular thickness of the radius [MD -0.01 (95 % CI: -0.02 – -0.00); P = 0.0006], tibia [MD -0.01 (95 % CI: -0.02 – -0.00); P=0.03] and cortical thickness of the radius [MD -0.01 (95 % CI: -0.19 – -0.00); P = 0.04] was significantly lower in patients with prolactinoma as compared to controls. The occurrence of fractures was significantly higher in patients with prolactinoma as compared to controls [OR 3.21 (95 % CI: 1.64 – 6.26); P = 0.0006] Conclusion: Bone mass is adversely affected in patients with hyperprolactinemia due to prolactinoma with predominant effects on the trabecular bone.

Meta-analysis of the effects of denosumab and romosozumab on bone mineral density and turnover markers in patients with osteoporosis.

To assess the alterations in bone mineral density and bone turnover marker concentrations following the administration of denosumab and romosozumab therapies in patients with osteoporosis. PubMed was searched for studies published until January 28, 2023, that investigated the clinical efficacy and bone turnover marker changes of denosumab and romosozumab in the treatment of osteoporosis, with a minimum follow-up of 3 months in each study. Studies were screened, and data on changes in bone mineral density (BMD), P1NP, and TRACP-5b levels after treatment were extracted and included in the analysis. Six studies were analyzed. At 3 months after treatment, the romosozumab group showed greater changes in lumbar BMD and bone turnover markers. BMD of total hip and femoral neck was relatively delayed. Beginning at 6 to 12 months, romosozumab showed greater changes in bone mineral density and markers of bone turnover. Both romosozumab and denosumab have antiosteoporotic effects, with greater effects on BMD and bone turnover markers observed within 12 months of romosozumab treatment. https://www.crd.york.ac.uk/prospero, identifier CRD42023395034.

Improved bone and renal safety in younger tenofovir disoproxil fumarate experienced chronic hepatitis B patients after switching to tenofovir alafenamide or entecavir

Introduction and ObjectivesRenal and bone impairment has been reported in chronic hepatitis B (CHB) patients receiving long-term tenofovir disoproxil fumarate (TDF) therapy. This study aimed to assess the incidence of renal and bone impairment in CHB patients with long-term TDF therapy and to identify the changes in bone mineral density (BMD) and renal function in these patients after switching to entecavir (ETV) or tenofovir alafenamide (TAF). Materials and MethodsThis retrospective study collected clinical data from CHB patients who received TDF monotherapy over 96 weeks. The changes in BMD and renal function were analyzed after 96 weeks of switching antiviral regimens (ETV or TAF) or maintenance TDF. ResultsAt baseline, 154 patients receiving TDF monotherapy over 96 weeks were enrolled, with a younger median age of 36.75 years, 35.1% (54/154) of patients experienced elevated urinary β2 microglobulin and 20.1% (31/154) of patients had reduced hip BMD (T<-1). At week 96, among the 123 patients with baseline normal BMD, patients who maintained TDF (n=85) had experienced a decrease in hip BMD, while patients who switched antiviral regimens (n=38) experienced an increase (-13.97% vs 2.34%, p<0.05). Among patients with a baseline reduced BMD (n=31), the alterations in BMD were similar in patients who maintained TDF (n=5) and those who switched antiviral regimens (n=26) (-15.81% vs 7.35%, p<0.05). Irrespective of baseline BMD status, renal function decreased significantly in patients who maintained TDF and improved in patients who switched antiviral regimens. ConclusionsYounger CHB patients on long-term TDF therapy are at high risk for bone and renal impairment, with the risk being reduced when switched to ETV or TAF.

The Impact of Cholecaciferol Supplementation on Bone Mineral Density in Long-Term Kidney Transplant Recipients

Although reduced bone mineral density (BMD) is associated with a higher risk of fractures, morbidity, and mortality in kidney transplant patients (KTRs), there is no consensus on optimal treatment for the alterations of BMD in this population. This study aims at assessing the effect of cholecalciferol supplementation on BMD over a follow-up period of 2 years in a cohort of long-term KTRs. Patients with age ≥ 18 years were included and divided into two subgroups based on treatment with bisphosphonate and/or calcimimetics and/or active vitamin D sterols (KTRs-treated) or never treated with the above medications (KTRs-free). BMD was evaluated at lumbar vertebral bodies (LV) and right femoral neck (FN) with standard DEXA at the beginning and end of the study. According to World Health Organization (WHO) criteria, results were expressed as T-score and Z-score. Osteoporosis and osteopenia were defined as T score ≤ -2.5 SD and T score < -1 and >-2.5 SD, respectively. Cholecalciferol was supplemented at a dose of 25,000 IU/week over 12 weeks followed by 1500 IU/day. KTRs-free (n. 69) and KTRs-treated (n. 49) consecutive outpatients entered the study. KTRs-free were younger (p < 0.05), with a lower prevalence of diabetes (p < 0.05) and of osteopenia at FN (46.3 % vs. 61.2 %) compared to KTRs-treated. At the entry none of the study subjects had a sufficient level of cholecalciferol; Z-score and T-score at LV and FN were not different between groups. At the end of the study period, serum cholecalciferol concentration was significantly increased in both groups (p < 0.001); the KTRs-free group presented an improvement in both T-score and Z-score at LV (p < 0.05) as well as a lower prevalence of osteoporotic cases (21.7% vs. 15.9%); in contrast, no changes were recorded in KTR-treated individuals. In conclusion, supplementation with cholecalciferol ameliorated Z-score and T-score at LV in long-term KTRs who had been never treated with active or inactive vitamin D sterols, bisphosphonates, and calcimimetics. Future endeavours are needed to confirm these preliminary findings.

Long-Term Changes in Bone Density and Bone Metabolism After Gastric Bypass Surgery: a Retrospective Cohort Study.

Patients with severe obesity submitted to Roux-en-Y gastric bypass (RYGB) are at risk of developing long-term hypovitaminosis D and secondary hyperparathyroidism (SHPT) as well as osteometabolic disease. This study aimed to evaluate calcium-vitamin D-PTH axis and bone mineral density (BMD) changes from post-RYGB patients who were followed-up until a median of 5 years. Vitamin D deficiency was defined as 25-hydroxyvitamin D <20 ng/mL and SHPT as PTH >68 pg/mL, in patients with normal serum creatinine and calcium. BMD was estimated by dual-energy X-ray absorptiometry (DXA, g/cm2). We included 127 post-RYGB patients (51±10.6 years, 87.4% self-declared White, 91.3% female, 52.8% postmenopausal). Vitamin D deficiency prevalence was the highest (41.5%) in the second year and the lowest (21.2%) in the third year (p<0.05). SHPT prevalence was 65.4% in the second year and increased to 83.7% in the sixth year (p<0.05). Patients with low BMD in lumbar, femoral neck, and total proximal femur were older and presented menopausal status more frequently than normal BMD group (p<0.05). Older age was a risk marker for altered BMD in femoral neck (OR=1.185; 95% CI 1.118-1.256) and in total proximal femur (OR=1.158; 95% CI 1.066-1.258), both after adjusting for follow-up and excess weight loss. After 5 years, most bariatric patients presented calcium-vitamin D-PTH axis disruption, in which SHPT was more frequent than hypovitaminosis D. Older patients and menopausal women presented higher rates of low BMD, and older age was a risk marker, especially for low BMD in femoral sites.

Association of bone mineral density with prediabetes risk among African-American and European-American adult offspring of parents with type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is associated with alterations in bone mineral density (BMD), but association between prediabetes and BMD is unclear. We analyzed BMD among the initially normoglycemic participants in the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study in relation to incident prediabetes during 5 years of follow-up. A total of 343 participants (193 Black, 150 White) underwent DEXA during Year 1 of POP-ABC and were followed quarterly for 5 years. The mean age was 44.2 ± 10.6 years; BMI was 30.2 ± 7.23 kg/m2. At baseline, the mean BMD was 1.176 ± 0.135 g/cm2 (1.230 ± 0.124 g/cm2 in men vs. 1.154 ± 0.134 g/cm2 in women, P<0.0001; 1.203 ± 0.114 g/cm2 in Black vs. 1.146 ± 0.150 g/cm2 in White participants, P=0.0003). During 5 years of follow-up, 101 participants developed prediabetes and 10 subjects developed T2DM (progressors); 232 were nonprogressors. Progressors to prediabetes had numerically higher baseline BMD and experienced lower 1-year decline in BMD (P<0.0001) compared with nonprogressors. From Kaplan-Meier analysis, the time to 50% prediabetes survival was 2.15 y among participants in the lowest quartile of baseline BMD, longer than those in higher quartiles (1.31 - 1.41 y). Values for BMD correlated inversely with age and adiponectin levels, and positively with BMI. In logistic regression analysis, BMD z score significantly predicted incident prediabetes: more negative BMD z scores were associated with decreased incident prediabetes (odds ratio 0.598 [95% confidence interval 0.407 - 0.877], P=0.0085), after controlling for age, BMI, change in BMI, ethnicity, blood glucose and adiponectin. Among initially normoglycemic individuals, higher baseline BMD was associated with higher risk of incident prediabetes during 5 years of follow-up.

Distribution of Bone Mineral Density in the Ankle Joint: Correlation with Hindfoot Alignment

Category: Ankle; Basic Sciences/Biologics; Hindfoot Introduction/Purpose: Abnormal Hindfoot Alignment (HA) has been correlated with increased complication rates in ankle fusion or replacement. Altered Bone Mineral Density (BMD) due to abnormal stress distribution could be predisposing factor for those unwanted outcomes. The objective of this study was to assess spatial distribution of BMD around the ankle joint in patients with normal or abnormal HA using cone beam Weight Bearing CT. Methods: Retrospective comparative study including 81 ankles allocated into 3 groups based on the Foot Ankle Offset (FAO): 27 normal (0%5%). groups were comparable by age (p=0.967), Body Mass Idex (p=0.669), sex (p=0.820) and side (p=0.708). Semi- automatic segmentation (BoneLogic, Disior) was applied to identify bones. Tibia and talus were digitally compartmented in medial (M) and lateral (L) volumes relative to the median sagittal plane. Mean Hounsfield Unit (HU) value per compartment was used to assess BMD and to calculate the Medial over Lateral HU ratio (M/L-HU). Comparisons among the three groups were performed using one-way ANOVA, Kruskal-Wallis and Chi2 tests. Results: Mean +- standard deviation HU values in the compartments in normal cases were 495.2+-110 (medial tibia), 495.6+- 108.1 (lateral tibia), 368.9+-80.3 (medial talus), 448.2+-90.6 (lateral talus) and 686.7+-120.4 (fibula). Upon comparison of the mean BMD value for each compartment in the three groups, the difference did not achieve statistical significance. Conversely, the tibia HU-M/L ratio (0.88+-0.14 in valgus cases, 0.99 +- 0.08 in normally-aligned cases and 1.04+-0.08 in varus cases) and the talar HU- M/L ratio (0.68+-0.18 in valgus cases, 0.82+-0.08 in normally-aligned cases and 0.96+-0.20 in varus cases) were significantly different in the three groups (p&lt;0.001). Conclusion: We found that the BMD in distal tibia, fibula and the talus varies with hindfoot alignment. The increased HU medio- lateral ratio in varus cases was consistent with a greater medial bone density in the tibia and talus, while the decreased ratio found in valgus cases suggested a more lateral concentration in both bones. This data supports the role of WBCT in analyzing BMD distribution. This method could be clinically useful in ankle OA to evaluate bone quality for such considerations as surgical indications or implant positioning.

Protective effect of Spirulina against bone fragility induced by Garcinia cambogia in high-fat diet induced obese rats

The present work evaluated the protective effects of Spirulina against the bone fragility caused by Garcinia cambogia in high-fat diet induced obese rats. High-fat diet and high-fat emulsion (HFD+HFE) were administered via oral gavage to 30 six-week-old female Sprague Dawley rats for six weeks to induce obesity, except for a normal group (n = 6). Following four weeks of treatment, the diet-induced obese groups were orally administered, daily, with (1) G. cambogia (GC); (2) Spirulina (S); and (3) G. cambogia + Spirulina (GC+S). The normal and obese control groups were treated with equal volumes of 0.9% saline water. It was found that GC significantly decreased body mass index (BMI) below the obese range (0.68 g/cm2). Additionally, GC altered bone mineral density (BMD), increased phosphate and calcium levels, and decreased maximum force and mineral apposition rates (MAR) as compared to the obese control group (p &lt; 0.05). Bone fragility caused by GC was confirmed by the decrease in bone formation marker osteocalcin (OCN), as well as an increase in bone resorption receptor activator of nuclear factor kappa-B ligand (RANKL) and tartrate-resistant acid phosphatase type 5b (TRAP5b) as compared to the obese control group. Spirulina also decreased the BMI of the obese rats. Spirulina also increased blood bone markers, BMD, maximum force, and Young’s modulus. Rats supplemented with GC+S demonstrated higher double-labelled surface (dLS/BS) and MAR as compared to those in the GC group (p &lt; 0.05). Meanwhile, the S group demonstrated improvement in all dynamic histomorphometric indices. S and GC+S groups demonstrated bone formation upregulation and bone resorption downregulation, thus indicating a bone protective effect of Spirulina. Overall, GC treatment led to bone fragility. GC+S treatment significantly augmented bone formation and mineralisation in obese rats as compared to the GC treatment alone. Rats in the S group demonstrated effective weight reduction while showing no destructive effects on the bone.

Effects of Muscles on Bone Metabolism-with a Focus on Myokines.

Skeletal muscles and bones, the largest tissues in the body of a non-obese person, comprise the musculoskeletal system, which allows mobility and protects internal organs. Although muscles and bones are closely related throughout life, observations during development and aging and in human and animal disuse models have revealed the synchronization of tissue mass such that muscle phenotype changes precede alterations in bone mineral density and strength. This review discussed that mechanical forces, which have been the traditional research focus, are not the only mechanism by which muscle-derived signals may affect bone metabolism and emphasized the significance of skeletal muscles as an endocrine organ that secretes bone-regulatory factors. Consequently, both mechanical and biochemical aspects should be considered to fully understand muscle–bone crosstalk. This review also suggested that specific myokines could be ideal therapeutic targets for osteoporosis to both increase bone formation and reduce bone resorption; moreover, these myokines could also be potential circulating biomarkers to predict musculoskeletal health.

1203-P: Association of Bone Mineral Density (BMD) with Prediabetes in a Biracial Cohort

Background: Type 2 Diabetes (T2D) is associated with alterations in BMD, but association between prediabetes and BMD is less clear. Subjects and Methods: We analyzed BMD in relation to demographic and metabolic parameters among the initially normoglycemic offspring of T2D parents in the POP-ABC (Pathobiology of Prediabetes in a Biracial Cohort) study. We further assessed the relationship between BMD and the risk of progression to prediabetes during 5 years of follow-up. Results: A total of 376 participants underwent DEXA (Dual-energy X-ray absorptiometry) during Year 1 of POP-ABC and were followed quarterly for 5 years, the primary outcome being progression from normoglycemia to prediabetes. The mean age was 44.2 ± 10.6 years; BMI was 30.2 ± 7.23 kg/m2; 217 Black, 159 White, with 71% female. At baseline, the mean BMD was 1.176 ± 0.135 g/cm2 for the entire cohort; 1.230 ± 0.124 g/cm2 in men vs. 1.154 ± 0.134 g/cm2 in women (P&amp;lt;0.0001) ; 1.203 ± 0.114 g/cm2 in Black vs. 1.146 ± 0.150 g/cm2 in White participants (P=0.0003) . There was an inverse relationship between BMD and age (r= −0.254, P&amp;lt;0.0001) and a direct association with BMI (r=0.173, P=0.0028) and weight (r=0.315, P&amp;lt;0.0001) . The BMD showed no significant correlation with insulin secretion or insulin sensitivity. However, the BMD z score, which compares BMD to the average values for a person of same age and gender, was significantly correlated with risk of progression to prediabetes (r = 0.173, P=0.0029) and showed positive association with total body fat mass (r=0.208, p=0.0003) and trunk fat mass (r= 0.178, P= 0.0021) . BMD z score was not significantly correlated with either CRP or adiponectin level. Conclusion: Among POP-ABC participants, BMD had the expected relationships with age, sex, and race. Higher BMD z score was predictive of progression to prediabetes among initially normoglycemic offspring of T2D parents during 5-year follow-up, an association that requires further mechanistic insights. Disclosure Z.Liu: None. A.A.Patel: None. S.Dagogo-jack: Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Medtronic, Merck &amp; Co., Inc., Sanofi. Funding American Diabetes Association (7-07-MN-13) ; National Institutes of Health (RDK067269)

Case series of orthopaedic complications associated with endocrine disorders presented at tertiary care center and review of literature

&lt;p class="abstract"&gt;Endocrine glands affecting skeletal system are parathyroid glands, adrenal glands, pituitary gland, thyroid and gonads. If any abnormality occurs in these glands, they cause structural and functional impairment of the skeletal system. Early diagnosis and treatment of these endocrine problems and ruling out musculoskeletal involvement helps to maintain skeletal integrity and prevent osteoporotic fractures and chronic bone pathologies. Here we present a case series of 4 patients who came to us with chronic bone pathologies or post-traumatic fractures associated with endocrine abnormalities­; such as parathyroid adenoma (hyperparathyroidism), Cushing’s syndrome and thyroid adenocarcinoma. One patient with osteoporotic and pathological fracture was managed operatively and sent for management of endocrine pathology and other three patients after evaluating cause for the bone pathology were referred for primary management of endocrine disease.&lt;strong&gt; &lt;/strong&gt;Osteoclasts and osteoblasts of the bone are affected by the endocrine hormones, such as parathyroid hormone, thyroid, glucocorticoids and gonadotropins. Any abnormality in these hormones leads to alteration of bone mineral density. Hyperthyroidism, glucocorticoid excess, hyperparathyroidism, hypogonadism, and acromegaly decrease bone mineral density and aggravate the osteoporotic tendencies and leading to orthopaedic complications. As an orthopaedic practitioner we should be well aware of endocrine disorders affecting bones. Early diagnosis and treatment of these endocrine problems in older patients helps to maintain their skeletal integrity, prevent osteoporotic fracture and orthopaedic complications.&lt;/p&gt;