Decline In Bone Mineral Density Research Articles

Abstract PO1-12-10: Zoledronic acid to prevent rebound fractures after stopping adjuvant denosumab: a randomized controlled sub-study of the ABCSG-18 trial

Abstract Introduction ABCSG-18 trial showed that 60mg denosumab subcutaneously every 6 months halves fracture risk in postmenopausal patients with early breast cancer, who are treated with adjuvant aromatase inhibitors. However, it has been reported that stopping denosumab may lead to overactivation of osteoclasts resulting in so called rebound vertebral fractures. As shown previously, zoledronic acid (ZA), when given to patients of the ABCSG-18 trial after stopping denosumab prevents a high bone turnover state that can occur in some patients. Here we report the impact of a single ZA dose on bone mineral density (BMD) and fractures after stopping denosumab. Methods ABCSG-18 trial patients, who had received adjuvant denosumab were re-randomized to receive a single dose of ZA 5mg i.v. or not, 8 months +- 4 weeks after their last denosumab dose. DXA scans, lateral spine X-rays and bone turnover markers (CTX and osteocalcin) were assessed at baseline and at 6, 12 and 18 months thereafter. New clinical fractures were assessed until 18 months after randomization. Results 50 patients were randomized to either ZA (24pts) or control (26pts). All patients of the ZA arm and 25 out of 26 patients of the control arm had received 7 doses of denosumab within the ABCSG 18 trial before re-randomization. Baseline bone health factors were well balanced between the 2 arms: Baseline BMD did not differ between the two arms with regard to femoral neck (ZA: 0.817 g/cm2; SOC: 0.816g/cm2), total hip (ZA: 0.918g/cm2; SOC: 0.921g/cm2) and lumbar spine (ZA: 1.128 g/cm2; SOC 1.142 g/cm2), respectively. Relative changes in BMD differed significantly between both arms for femoral neck after 12 months (ZA: 0.5%; control: -4.98%, p 0.004) and for total hip after 6 months (ZA: -0.73%; control: -4.61%, p< 0.001) and after 12 months (ZA: -0.13%; control: -5.62%; p< 0.001). There was a trend towards a greater decline in BMD at lumbar spine after 6 months in the control arm versus the ZA arm (-3.35% vs 0.67%, p=0.052). After randomization, 3 asymptomatic fractures (lumbar vertebral and thoracic vertebral in one patient and thoracic vertebral in a second patient) occurred in the ZA arm, whereas 2 clinical fractures (one radius fracture and one lumbar vertebral fracture) occurred in the SOC arm. Conclusion A single dose of Zoledronic acid prevents high bone turnover state resulting in loss of BMD in some patients after stopping denosumab. ZA may therefore be offered to breast cancer patients with aromatase inhibitor after stopping denosumab. Citation Format: Georg Pfeiler, Christian F. Singer, Dominik Hlauschek, Manfreda Diether, Ferdinand Haslbauer, Paul Sevelda, Kristin Köck, Karl Tamussino, Arno C. Reichenauer, Florian Fitzal, Dietmar Heck, Richard Greil, Claudia Pasterk, Sonja Heibl, Walter Herz, Marija Balic, Daniel Egle, Lidija Sölkner, Michael Gnant. Zoledronic acid to prevent rebound fractures after stopping adjuvant denosumab: a randomized controlled sub-study of the ABCSG-18 trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-12-10.

Factors influencing periprosthetic bone mineral density in total knee arthroplasty: a systematic review.

Following total knee arthroplasty (TKA), there is a significant decline in periprosthetic bone mineral density (BMD), potentially resulting in complications such as prosthetic loosening, periprosthetic fracture, and influencing the postoperative recovery. The objective of this study was to summarize the factors influencing periprosthetic BMD in TKA from existing studies. A comprehensive systematic search was performed in 4 databases: Pubmed, Embase, Web of Science, and Cochrane Library. The last search was carried out on October 12, 2023. We used the keywords ''total knee arthroplasty'', ''bone mineral density'' and each of them combined with ''tibia'' and ''femur'' to identify all relevant articles reporting about potential impact factors influencing the periprosthetic BMD in patients after TKA. Out of 1391 articles, 22 published from 2001 to 2023 were included in this systematic review. Following eligibility screening, six significant categories affecting periprosthetic BMD were recognized: prosthesis type, design of stem, coating, body weight, cement, and peg distance. Mobile-bearing prostheses, modular polyethylene design, short stems, cruciform stems, avoidance of bone cement, higher body mass index, titanium nitride coating, and a smaller medial peg distance could potentially benefit periprosthetic BMD. Comprehensive consideration of diverse factors influencing periprosthetic BMD before surgery and collaboration with post-operative drug therapy are essential. The PROSPERO registration number is CRD42023472030.

Mitofusin 2 plays a critical role in maintaining the functional integrity of the neuromuscular-skeletal axis

PurposeMitofusin 2 (Mfn2) is one of two mitofusins involved in regulating mitochondrial size, shape and function, including mitophagy, an important cellular mechanism to limit oxidative stress. Reduced expression of Mfn2 has been associated with impaired osteoblast differentiation and function and a reduction in the number of viable osteocytes in bone. We hypothesized that the genetic absence of Mfn2 in these cells would increase their susceptibility to aging-associated metabolic stress, leading to a progressive impairment in skeletal homeostasis over time. MethodsMfn2 was selectively deleted in vivo at three different stages of osteoblast lineage commitment by crossing mice in which the Mfn2 gene was floxed with transgenic mice expressing Cre under the control of the promoter for Osterix (OSX), collagen1a1, or DMP1 (Dentin Matrix Acidic Phosphoprotein 1). ResultsMice in which Mfn2 was deleted using DMP1-cre demonstrated a progressive and dramatic decline in bone mineral density (BMD) beginning at 10 weeks of age (n = 5 for each sex and each genotype from age 10 to 20 weeks). By 15 weeks, there was evidence for a functional decline in muscle performance as assessed using a rotarod apparatus (n = 3; 2 males/ 1 female for each genotype), accompanied by a decline in lean body mass. A marked reduction in trabecular bone mass was evident on bone histomorphometry, and biomechanical testing at 25 weeks (k/o: 2 male/1 female, control 2 male/2 female) revealed severely impaired femur strength. Extensive regional myofiber atrophy and degeneration was observed on skeletal muscle histology. Electron microscopy showed progressive disruption of cellular architecture, with disorganized sarcomeres and a bloated mitochondrial reticulum. There was also evidence of neurodegeneration within the ventral horn and roots of the lumbar spinal cord, which was accompanied by myelin loss and myofiber atrophy. Deletion of Mfn2 using OSX-cre or Col1a1-cre did not result in a musculoskeletal phenotype. Where possible, male and female animals were analyzed separately, but small numbers of animals in each group limited statistical power. For other outcomes, where sex was not considered, small sample sizes might still limit the strength of the observation. ConclusionDespite known functional overlap of Mfn1 and Mfn2 in some tissues, and their co-expression in bone, muscle and spinal cord, deletion of Mfn2 using the 8 kB DMP1 promoter uncovered an important non-redundant role for Mfn2 in maintaining the neuromuscular/bone axis.

Loss of chaperone-mediated autophagy does not alter age-related bone loss in male mice.

Chaperone-mediated autophagy (CMA) is a lysosome-dependent degradation pathway that eliminates proteins that are damaged, partially unfolded, or targeted for selective proteome remodeling. CMA contributes to several cellular processes, including stress response and proteostasis. Age-associated increase in cellular stressors and decrease in CMA contribute to pathologies associated with aging in various tissues. CMA contributes to bone homeostasis in young mice. An age-associated reduction in CMA was reported in osteoblast lineage cells; however, whether declining CMA contributes to skeletal aging is unknown. Herein we show that cellular stressors stimulate CMA in UAMS-32 osteoblastic cells. Moreover, the knockdown of an essential component of the CMA pathway, LAMP2A, sensitizes osteoblasts to cell death caused by DNA damage, ER stress, and oxidative stress. As elevations in these stressors are thought to contribute to age-related bone loss, we hypothesized that declining CMA contributes to the age-associated decline in bone formation by sensitizing osteoblast lineage cells to elevated stressors. To test this, we aged male CMA-deficient mice and controls up to 24 months of age and examined age-associated changes in bone mass and architecture. We showed that lack of CMA did not alter age-associated decline in bone mineral density as measured by dual x-ray absorptiometry (DXA). Moreover, microCT analysis performed at 24 months of age showed that vertebral cancellous bone volume, cortical thickness, and porosity of CMA-deficient and control mice were similar. Taken together, these results suggest that reduction of CMA does not contribute to age-related bone loss.

Impact of sprint training on bone health: a literature review of current evidence

Specific impact of sprint training (ST) on bone health has yet to be fully explored, in particular how it affects bone mineral density (BMD) and bone structure.Aim. To investigate the ST and bone health relationship between athletes of different training intensities and nonathletes of different ages.Materials and methods. A search of databases PubMed, Embase, and Pedro was conducted from January 2009 to August 2023. The full texts of all potentially relevant studies were obtained and evaluated by three independent reviewers for inclusion.Results. The comprehensive review of eight studies indicates a positive influence of ST on bone health. Sprinters show higher cortical and trabecular BMD in the tibia than controls, with a noted age-related decline in BMD. Short distance runners demonstrate significantly better BMD, counter-movement jump performance, and grip strength compared to long-distance runners. These benefits are consistent across various age groups, including older athletes, with minimal age-related changes in mid-tibial BMD. ST is also associated with a 21% increase in tibial stress-strain index, indicating sustained bone strength, and a reduction in fracture risk in the elderly through downregulation of fracture-related microRNAs.Conclusion. ST significantly enhances bone health, particularly in improving BMD and bone microarchitecture. Incorporating ST into exercise routines may benefit athletes and older individuals. Further research is essential to understand the mechanisms and develop optimal training protocols for bone health.

Biological/targeted synthetic DMARDs do not arrest bone loss in patients with rheumatoid arthritis: a multicenter prospective observational study

Abstract Objective To elucidate the differential effects of biological/target synthesized DMARDs (b/tsDMARDs) on bone metabolism in patients with rheumatoid arthritis (RA) in a real-world cohort. Methods This was a multicentre prospective observational study of RA patients enrolled at the time of first b/tsDMARDs administration. Bone mineral density (BMD) and bone turnover markers (BTMs) were measured during the 52-week observation. The study was designed to enrol all eligible RA patients. The end-points were differences in changes in BMD according to b/tsDMARD type, and the correlation between BMD and BTMs. Results A total of 1164 patients were enrolled in this study. b/tsDMARDs improved RA disease activity from mean CDAI 25.5 at baseline to 4.5 at week 26. Patients not receiving anti-osteoporotic agents (anti-OP) at baseline with no history of fracture experienced a significant decrease in both femoral neck (F: mean 0.666–0.655 g/cm3) and radial (R: 0.518–0.514) BMD at week 26. Despite maintaining low CDAI levels during weeks 26–52 (5.3–4.4), there was a continued decline in BMD (F: 0.653, R: 0.509. Weeks 52). None of the b/tsDMARDs type preserved BMD. Conversely, patients receiving anti-OP at baseline maintained stable BMD throughout the study (Weeks 0/26/52. F: 0.551/0.551/0.555, R: 0.415/0.416/0.415). Although BTMs were changed by b/tsDMARDs, the changes were unrelated to those in BMD. Conclusion Our study suggested the progression of osteoporosis in RA patients during b/tsDMARDs treatment without anti-OP. BTMs may not reflect BMD change. Regular monitoring of BMD in RA should be considered for early management of osteoporosis.

Effect of Pelvic External Beam Radiation Therapy on Bone Mineral Density: A Secondary Analysis of a Phase 3 Randomized Controlled Trial

Pelvic radiation therapy may lead to decreased bone mineral density (BMD) and increased risk of fracture that could be of particular concern in patients with prostate cancer who also receive androgen deprivation therapy (ADT). We performed an exploratory analysis of a randomized, double-blind, placebo-controlled trial to determine whether exposure to prior pelvic external beam radiation therapy (XRT) affects BMD and risk of fracture in patients with prostate cancer treated with ADT. Patients with nonmetastatic prostate cancer aged ≥70 years or <70 years with low BMD (T-score < -1) or osteoporotic fracture who had been receiving ADT for ≥12 months were randomly assigned to receive densoumab or placebo every 6 months for 3 years. BMD was measured at baseline and at months 1, 3, 6, 12, 24, and 36. We applied multivariable linear mixed-effects models with an interaction term between the treatment arm and exposure to prior pelvic XRT to evaluate differential XRT effect on percent BMD change between the 2 treatment arms. Among 1407 eligible patients, 31% (n=447) received prior pelvic XRT. There was no significant difference in any clinical fractures among patients with (5.8%, 26 of 447) or without (5.2%, 50 of 960) prior pelvic XRT (P=.42). Prior pelvic XRT was associated with a significant (0.54%) improvement in BMD (95% CI, 0.05-1.02) in the placebo group and a nonsignificant (0.04%) decline in BMD (95% CI, -0.47 to -0.35) in the denosumab group (interaction P=.007). There was no significant difference in pelvic XRT effect on percent BMD change in the lumbar spine (P=.65) or total hip (P=.39) between the 2 treatment groups. We did not find sufficient evidence to suggest any detrimental effect of pelvic XRT on the treatment effect from denosumab on percent BMD change, with only an approximately 5% incidence of clinical fractures.

Changes in femoral neck bone mineral density and structural strength during a 12-month multicomponent exercise intervention among older adults – Does accelerometer-measured physical activity matter?

Age-related bone loss is to some extent unavoidable, but it may be decelerated with regular exercise continued into older age. Daily physical activity alongside structured exercise may be an important stimulus for maintaining bone strength, but the relationships of habitual physical activity with bone strength are sparsely investigated in older adults. Therefore, the main aim was to investigate if accelerometer-derived impact-based and intensity-minute-based measures of physical activity were associated with changes in femoral neck bone traits during a 12-month exercise intervention among community-dwelling older men and women.Data comes from the PASSWORD study (ISRCTN52388040), a year-long multicomponent exercise intervention. Participants were 299 older adults (mean age 74 ± 4 years, 58 % women), who self-reported not to meet the physical activity guidelines for older adults but did not have any contraindications for exercising. The multicomponent training program included both supervised and self-administered exercises aimed at improving muscle strength, postural balance, and aerobic endurance. Physical activity was assessed at baseline and at six months into the intervention, and femoral neck bone properties at baseline and at twelve months. Physical activity measures were accelerometer-measured mean daily osteogenic index score, low, medium, and high intensity impact counts, and sedentary, light, and moderate-to-vigorous intensity activity minutes. Femoral neck bone mineral density (BMD) was measured with DXA and structural strength indicators (cross-sectional area [CSA] and section modulus) were subsequently derived from hip structural analysis. Longitudinal associations of physical activity and bone outcomes were analyzed with generalized estimating equation linear models. Sex was included as a moderating factor, and models were further adjusted by potentially confounding factors (age, height, weight, smoking status, medications, chronic disease conditions, and strength training adherence).Participants increased their physical activity by all measures and decreased their sedentary time from baseline to six months. BMD decreased from baseline to post-intervention, while CSA maintained stable and section modulus slightly increased. Osteogenic index, high impacts, and moderate-to-vigorous intensity physical activity, measured across the first half of the study, were positively associated with changes in BMD over 12 months (time х physical activity interaction effect: ß = 0.065, 95 % CI [0.004, 0.126]; ß = 0.169, 95 % CI [0.048, 0.289]; and ß = 0.151, 95 % CI [0.016, 0.286], respectively). That is, the higher the physical activity was, the smaller was the decline in BMD. Any physical activity measure was not associated with changes in CSA or section modulus in the full study sample. Sex did not significantly moderate the longitudinal associations, except the association between sedentary time and CSA (sex х time х PA interaction effect: ß = −0.017, 95 % CI [−0.033, −0.002]). An inverse association was found between sedentary time and changes in CSA in women, but not in men.In conclusion, BMD decline was less pronounced in individuals who accumulated more accelerometer-measured daily physical activity at the intensity of very brisk walking or light lateral jumping or higher intensities in a sample of relatively healthy, previously physically inactive older adults. Our findings support that accumulating the recommended amount of 150 or more weekly minutes of moderate-to-vigorous physical activity is also beneficial for older adults' bone health when incorporated into a multicomponent exercise program.

OR13-05 Longitudinal Changes In Bone Turnover Following Withdrawal Of RANKL Inhibition

Abstract Disclosure: A.S. Kim: None. A. Castro-Martinez: None. V. Taylor: None. J. Center: None. C.M. Girgis: None. P.I. Croucher: None. M.M. Mcdonald: None. Denosumab is an effective osteoporosis treatment, preventing bone loss by inhibiting RANKL. However, stopping denosumab leads to rebound bone mineral density(BMD) loss. This is due to accelerated bone resorption by osteoclasts. Serum bone turnover markers such as P1NP and CTX have been utilised in clinical practice to guide sequential therapy following denosumab discontinuation. However, an optimal strategy has not been established. Understanding the temporal changes in osteoclast activity will guide safe, effective sequential therapy following denosumab discontinuation. We hypothesised that serum TRAP5b, a marker of enzymatic activity of osteoclasts, would be a more useful marker in this context to guide sequential treatment following denosumab discontinuation. Seven-week-old female C57BL/6 mice were treated with 2-weeks of thrice-weekly OPG:Fc(10mg/kg) to inhibit RANKL then withdrawn from therapy (OPG-W) or saline(vehicle). Longitudinal BMD and serum TRAP5b were measured throughout the study. Mice were harvested at weeks 2, 8, 11 and 13 to allow a large volume of serum to be collected to concurrently measure serum TRAP5b and the products of collagen formation and breakdown, serum P1NP and CTX respectively . Following OPG:Fc withdrawal, BMD peaked at week 8 in OPG-W mice (92.94 vs75.09mg/cm2, p&amp;lt;0.0001), started to decline at week 10 and normalised to vehicle levels by week 13. Longitudinally, serum TRAP was suppressed by week 2 (0.05 vs 11.90U/L, p&amp;lt;0.0001) and remained suppressed until week 8, following which serum TRAP levels rose progressively to 64% above vehicle levels at week 12 (17.86 vs 10.92U/L, p&amp;lt;0.0001). The rise in TRAP between weeks 8 to 10 preceded the decline in BMD.Serum TRAP was significantly elevated in OPG-W mice at week 11 (15.45 vs 11.46U/L, p=0.01) whereas serum P1NP and CTX remained equivalent to vehicle levels. Serum TRAP, P1NP and CTX were significantly higher in OPG-W mice at week 13 by which time BMD had reached vehicle levels. Our findings show that rebound decline in BMD has already occurred by the time bone turnover markers used in clinical practice (P1NP and CTX) rise above vehicle levels. A significant overshoot in serum TRAP occurs earlier and prior to bone loss and may better inform sequential therapy following denosumab discontinuation. Presentation: Friday, June 16, 2023

THU445 Complicated Course And Management After Denosumab Discontinuation: A Case Report

Abstract Disclosure: I. Arora: None. L. Ceglia: None. Background: Discontinuation of denosumab (DMAb) can lead to rapid bone loss and sometimes multiple vertebral fractures (VFx). Here we present such a case and related challenges in management. Case: A 56-year-old perimenopausal female presented for management of osteoporosis (OP) complicated by multiple VFx following a missed dose of DMAb in 8/2020. Past bone health history was notable for treatment with alendronate for approximately 11 years as a premenopausal woman. During a drug “holiday” in 2015, she was found to have a decline in bone mineral density (BMD). She was advised to start treatment with DMAb in 8/2016. She was adherent to DMAb injections for 4 years but missed a dose in 8/2020 due to the COVID-19 pandemic. In 1/2021, she developed back pain with no trauma and was diagnosed with VFx of T7, T10 and T12. She underwent vertebroplasty of all 3 vertebrae by 2/2021. DMAb was resumed in 2/2021 and 8/2021. Labs were only notable for hypercalciuria for which hydrochlorothiazide (HCTZ) was initiated. In 11/2021 she presented with new symptomatic VFx of T5, T9 and T11. In 12/2021 (3 weeks post 3 new VFx), serum fasting C-telopeptide (CTX) was 79 pg/mL. Teriparatide or abaloparatide were avoided due to hypercalciuria and potential BMD losses with this transition. Thus in 1/2022, she started romosozumab (ROMO) in an attempt to prevent new VFx. CTX was initially 78 pg/mL and rose rapidly over 3 months to 325 pg/mL with new back pain in 4/2022. No new VFx were detected; however, ROMO was discontinued due to the rise in CTX level. In 5/2022, she received a dose of zoledronic acid (ZOL). It suppressed CTX from 325 to 131 pg/mL by 6/2022. She received another 2 doses of ZOL in 8/2022 and 11/2022 due to rebound rises in CTX. Of note, as she reported ongoing menopausal complaints, transdermal low-dose estradiol therapy was started in 11/2022. She has not had a new VFx in more than 1 year. Hypercalciuria persisted throughout 2022 requiring rising doses of (HCTZ). DXA in 12/2022 was stable vs. 12/2021 without evidence of significant BMD loss. Discussion: This case not only highlights the known risk for multiple VFx in a patient discontinuing long-term DMAb treatment (4 years), but also the risks for such VFx complications in women of younger age during menopausal transition and a history of vertebroplasty. In addition, this report does not support transitioning from long-term DMAb to ROMO in order to prevent a rapid increase in the bone resorption marker, CTX. Rather, treatment with ZOL every 12 weeks based on frequent CTX monitoring successfully maintained BMD stable following long-term DMAb discontinuation. Presentation: Thursday, June 15, 2023

The Effect of Antihypertensive Therapy on Skeletal Muscle Mass and Bone Mineral Density in Patients With End-Stage Kidney Disease

ObjectiveSarcopenia and osteoporosis substantially influence health and lifespan. However, the variables affecting skeletal muscle mass (SMM) or bone mineral density (BMD) remain unknown. Design and MethodsFrom August 1, 2018, to July 31, 2019, we conducted a single-center, observational cohort study with 291 Japanese adult patients on maintenance hemodialysis due to end-stage kidney disease (ESKD), who had their femoral neck BMD measured using dual-energy X-ray absorptiometry. After 1-year follow-up, we measured annual changes of BMD (ΔBMD) and SMM (ΔSMM), which was calculated through a modified creatinine index (mg/kg/day) using age, sex, serum creatinine, and single-pooled Kt/V for urea. The factors associated with ΔSMM/ΔBMD or progressive loss of SMM/BMD, defined as ΔSMM/ΔBMD <0 per year respectively, were analyzed with multivariable, linear regression or logistic regression models. ResultsThe median age of the patients was 66 years and 33% were female. Dialysis vintage and β-blocker-use were inversely correlated to ΔSMM. In comparison to nonusers, β-blockers users had 2.5-fold-higher SMM loss odd ratios [95% confidence interval (CI), 1.3–4.8]. The risk for SMM loss caused by β-blockers was not increased in users of renin-angiotensin system inhibitors (RASis). The ΔBMD was negatively correlated to the usage of calcium channel blockers (CCBs). The risk of developing osteosarcopenia, which was defined as annual loss of both SMM and BMD, increased in CCBs users. ConclusionThe use of β-blockers is associated with an elevated risk of developing sarcopenia, whereas RASis may minimize this effect in patients with ESKD. The CCB therapy was associated with a faster decline of BMD.

Considerations on implementation of the newest treatment for symptomatic uterine fibroids: Oral GnRH antagonists.

Novel gonadotrophin releasing hormone (GnRH) antagonist treatments have recently been developed in combination with hormonal add-back therapy, as an oral treatment option for women suffering from uterine fibroids. Registration trials assessing the GnRH antagonist combination preparations with relugolix, elagolix and linzagolix have assessed treatment efficacy for fibroid-related heavy menstrual blood loss in comparison to placebo. Marketing authorization has been granted by several agencies including those in Europe, the United Kingdom and the United States. While the registration trials report a robust effect on the reduction of heavy menstrual blood loss and improvement in quality of life scores, reticence is advised before widespread prescription. In this review, we demonstrate limitations in the trial data, namely a lack of generalizability due to the restricted study population, the lack of transparency in the distribution of disease-level characteristics limiting the predictability of treatment success in the real-world diverse population, and the absence of any comparison to current alternative treatment methods. Importantly, no clinically meaningful volume reductions were found with GnRH antagonist combination preparations, and long-term safety data, particularly concerning modest but stable bone mineral density decline, need further addressing. Symptoms related to uterine fibroids adversely affect many women's quality of life and effective medical treatments are lacking. However, despite the urgent need for conservative treatments, it is vitally important that novel drugs, like combination oral GnRH antagonists, undergo sufficiently rigorous evaluation of safety, effectiveness and cost-effectiveness in a representative population and are compared with alternative treatment methods before introduction into mainstream clinical practice.

Understanding the characteristics of idiopathic osteoporosis by a systematic review and meta-analysis.

To understand the pathophysiology of idiopathic osteoporosis (IOP) better, we conducted a systematic review and meta-analysis of bone mineral density (BMD), hormones, and bone turnover markers (BTMs) between IOP patients and healthy controls. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, an appropriate search query was created, and three databases, including PubMed, ScienceDirect, and Google Scholar, were searched for screening relevant original articles. Feasible information, both qualitative and quantitative, was extracted and used to conduct meta-analyses. Publication bias and heterogeneity among studies were evaluated using appropriate statistical tools. A total of 21 studies were included in the meta-analysis. There was reduced BMD at the lumbar spine (LS) (pooled: SDM: -2.38, p-value: 0.0001), femoral neck (FN) (pooled: SDM: -1.75 p-value: 0.0001), total hip (TH) (pooled: SDM: -1.825, p-value: 0.0001) and distal radius (DR) (pooled: SDM of -0.476, p-value: 0.0001), of which LS was the most affected site. There was no significant change in BTMs compared with healthy controls. Total estradiol (SDM: -1.357, p-value: 0.003) was reduced, and parathyroid hormone (PTH) (SDM: 1.51, p-value: 0.03) and sex hormone-binding globulin (SHBG) (SDM: 1.454, p-value: 0.0001) were elevated in IOP patients compared with healthy controls. Our meta-analysis, the first of its kind on IOP, defines it as showing BMD decline maximally at LS compared with healthy controls without any alterations in the BTMs. Further studies are required to understand gender differences and the significance of altered hormonal profiles in this condition.

Computed tomography assessment of pelvic bone density: Associations with age and pelvic fracture in motor vehicle crashes

Motor vehicle crash (MVC) occupants routinely get a computed tomography (CT) scan to screen for internal injury, and this CT can be leveraged to opportunistically derive bone mineral density (BMD). This study aimed to develop and validate a method to measure pelvic BMD in CT scans without a phantom, and examine associations of pelvic BMD with age and pelvic fracture incidence in seriously injured MVC occupants from the Crash Injury Research and Engineering Network (CIREN) study. A phantom-less muscle-fat calibration technique to measure pelvic BMD was validated using 45 quantitative CT scans with a bone calibration phantom. The technique was then used to measure pelvic BMD from CT scans of 252 CIREN occupants (ages 16+) in frontal MVCs who had sustained either abdominal or pelvic injury. Pelvic BMD was analyzed in relation to age and pelvic fracture incidence. In the validation set, phantom-based calibration vs. phantom-less muscle-fat calibration yielded similar BMD values at the anterior superior iliac spine (ASIS; R2 = 0.95, p < 0.001) and iliac crest (R2 = 0.90, p < 0.001). Pelvic BMD was measured in 150 female and 102 male CIREN occupants aged 16–89, and 25% of these occupants sustained pelvic fracture. BMD at the ASIS and iliac crest declined with age (p < 0.001). For instance, iliac crest BMD decreased an average of 25 mg/cm3 per decade of age. The rate of iliac crest BMD decline was 7.6 mg/cm3 more per decade of age in occupants with pelvic fracture compared to those not sustaining pelvic fracture. Findings suggest pelvic BMD may be a contributing risk factor for pelvic fracture in MVCs.

OPG gene-modified adipose-derived stem cells improve bone formation around implants in osteoporotic rat maxillae

BackgroundOsteoporosis is a significant barrier to the use of dental implants in the elderly for the treatment of tooth defects. Adipose derived stem cells (ADSCs) have demonstrated extensive potential for tissue repair and regeneration. The present study aimed to investigate the effectiveness of ADSCs engineered to express high levels of osteoprotegerin (OPG) for the treatment of bone loss in implant dentistry caused by estrogen deficiency. MethodsA rat model of osteoporosis was established through double oophorectomy, and the rats were treated by gene modified cells Adv-OPG-ADSCs. The effects of the treatment on maxilla tissue changes were evaluated using HE staining and micro-CT. Additionally, ALP and TRAP staining were used to assess osteoblast and osteoclast alterations. Finally, the changes in related osteoblast and osteoclast indicators were measured by RT-qPCR, Western blot, and ELISA. ResultsThe successfully generated high-OPG-expressing ADSCs led to increase of cell viability, proliferation, and osteoblast differentiation. Treatment with Adv-OPG-ADSCs significantly ameliorated maxillary morphology, trabecular volume reduction, and bone mineral density decline in the model of estrogen-deficient maxillary implant dentistry. Furthermore, the treatment was beneficial to promoting the generation of osteoblasts and inhibiting the generation of osteoclast. Adv-OPG-ADSCs increased OPG, ALP, OCN, and Runx-2 expressions in the maxilla while suppressing RANKL expression, and also increased the concentration of COL I and PINP, as well as decreased the concentration of CTX-1. ConclusionAdv-OPG-ADSCs promote the formation of osteoblasts and inhibit the generation of osteoclasts, thereby inhibiting bone absorption, facilitating bone formation, and promoting the repair of maxillary bone after dental implantation in the presence of osteoporosis-related complications, especially in the setting of estrogen deficiency, providing scientific basis for the application of Adv-OPG-ADSCs in the treatment of implant related osteoporosis.

Potential alleviation of bone mineral density loss with Janus kinase inhibitors in rheumatoid arthritis.

Rheumatoid arthritis (RA) is characterized by localized bone loss, general osteoporosis and increased fracture risks. Tumour necrosis factor inhibitors (TNFi), non-tumour necrosis factor inhibitors (non-TNFi) biologic, Janus kinase inhibitors (JAKi) had shown the suppression effects to osteoclast activation and improvement of bone mineral density (BMD). Anti-cyclic citrullinated peptide antibody (ACPA) is associated with osteoclast activation and the resultant bone loss. However, few studies have compared BMD changes among patients with RA treated with targeted therapies that have different mechanisms of action. This retrospective study recruited patients with RA who had undergone BMD testing twice. Changes in the BMD were compared using the generalized estimating equation (GEE) in treatment groups that received conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), TNFi, non-TNFi biologics, and JAKi. In total, 362 patients with RA were enrolled (csDMARDs, n = 153, TNFi, n = 71, non-TNFi biologics, n = 108, JAKi, n = 30). We observed greater changes in femoral BMD (left, 0.06, 95% CI 0.01-0.12, p = 0.016; right, 0.09, 95% CI 0.04-0.15, p = 0.001 by GEE) following JAKi treatment as compared with other treatments. Compared to the ACPA-negative group, patients with ACPA positivity exhibited greater improvement in the femoral BMD (left, 0.09, 95% CI 0.02-0.15, p = 0.008; right, 0.11, 95% CI 0.05-0.18, p = 0.001). Compared to other targeted therapies, JAKi might exert a more potent effect to prevent BMD loss, specifically in ACPA-positive patients with RA, and could be a potential therapeutic option to mitigate generalized bone loss. Key Points •JAKi therapy inhibits systemic bone loss in patients with RA. •ACPA-positive RA patients exhibited a greater BMD improvement than ACPA-negative RA patients. •JAKi might more potently prevent BMD decline than conventional synthetic or biological DMARDs.

Protective Effect of Long-Term Fermented Soybeans with Abundant Bacillus subtilis on Glucose and Bone Metabolism and Memory Function in Ovariectomized Rats: Modulation of the Gut Microbiota.

We investigated the effects of different types of long-term fermented soybeans (traditionally made doenjang; TMD) on glucose and bone metabolism and memory function in ovariectomized (OVX) rats. The rats were categorized into six groups: Control, cooked unfermented soybeans (CSB), and four TMDs based on Bacillus subtilis (B. subtilis) and biogenic amine contents analyzed previously: high B. subtilis (HS) and high biogenic amines (HA; HSHA), low B. subtilis (LS) and HA (LSHA), HS and low biogenic amines (LA; HSLA), and LS and LA (LSLA). The rats in the CSB and TMD groups fed orally had a 4% high-fat diet for 12 weeks. Rats in the Control (OVX rats) and Normal-control (Sham-operated rats) groups did not consume CSB or TMD, although macronutrient contents were the same in all groups. Uterine weight and serum 17β-estradiol concentrations were much lower in the Control than the Normal-control group, but CSB and TMD intake did not alter them regardless of B. subtilis and biogenic amine contents. HOMA-IR, a measure of insulin resistance, decreased with TMD with high B. subtilis (HSLA and HSHA) compared to the Control group. In OGTT and IPGTT, serum glucose concentrations at each time point were higher in the Control than in the Normal-control, and HSLA and HSHA lowered them. Memory function was preserved with HSHA and HSLA administration. Bone mineral density decline measured by DEXA analysis was prevented in the HSHA and HSLA groups. Bone metabolism changes were associated with decreased osteoclastic activity, parathyroid hormone levels, and osteoclastic activity-related parameters. Micro-CT results demonstrated that TMD, especially HSLA and HSHA, preserved bone structure in OVX rats. TMD also modulated the fecal bacterial community, increasing Lactobacillus, Ligalactobacillus, and Bacillus. In conclusion, through gut microbiota modulation, TMD, particularly with high B. subtilis content, acts as a synbiotic to benefit glucose, bone, and memory function in OVX rats. Further research is needed to make specific recommendations for B. subtilis-rich TMD for menopausal women.

Vitamin D level in patients with systemic lupus erythematosus: its relationship to disease course and bone mineral density

ObjectiveTo determine vitamin D levels in patients with SLE and evaluate their relationship to bone mineral density (BMD) and the disease course.MethodsThe study included 101 patients with SLE and 29...

The Pathophysiology, Identification and Management of Fracture Risk, Sublesional Osteoporosis and Fracture among Adults with Spinal Cord Injury.

The prevention of lower extremity fractures and fracture-related morbidity and mortality is a critical component of health services for adults living with chronic spinal cord injury (SCI). Established best practices and guideline recommendations are articulated in recent international consensus documents from the International Society of Clinical Densitometry, the Paralyzed Veterans of America Consortium for Spinal Cord Medicine and the Orthopedic Trauma Association. This review is a synthesis of the aforementioned consensus documents, which highlight the pathophysiology of lower extremity bone mineral density (BMD) decline after acute SCI. The role and actions treating clinicians should take to screen, diagnose and initiate the appropriate treatment of established low bone mass/osteoporosis of the hip, distal femur or proximal tibia regions associated with moderate or high fracture risk or diagnose and manage a lower extremity fracture among adults with chronic SCI are articulated. Guidance regarding the prescription of dietary calcium, vitamin D supplements, rehabilitation interventions (passive standing, functional electrical stimulation (FES) or neuromuscular electrical stimulation (NMES)) to modify bone mass and/or anti-resorptive drug therapy (Alendronate, Denosumab, or Zoledronic Acid) is provided. In the event of lower extremity fracture, the need for timely orthopedic consultation for fracture diagnosis and interprofessional care following definitive fracture management to prevent health complications (venous thromboembolism, pressure injury, and autonomic dysreflexia) and rehabilitation interventions to return the individual to his/her pre-fracture functional abilities is emphasized. Interprofessional care teams should use recent consensus publications to drive sustained practice change to mitigate fracture incidence and fracture-related morbidity and mortality among adults with chronic SCI.

Denosumab effect on bone mineral density and urinary-NTX in breast cancer patients receiving aromatase inhibitors.

Aromatase inhibitors are used post-surgical intervention in postmenopausal patients with breast cancer. However, these drugs accelerate decline in bone mineral density (BMD), which is countered by use of denosumab, and the efficacy of the drug can be assessed by bone turnover markers. We investigated the effects of denosumab administration for 2years on BMD and urinary N-telopeptide of type I collagen (u-NTX) levels in breast cancer patients treated with aromatase inhibitors. This was a single-center retrospective study. Postoperative hormone receptor-positive breast cancer patients with low T-scores biannually received denosumab from the time of initiation of aromatase inhibitor therapy for 2years. BMD was measured every 6months, and u-NTX levels were assessed after 1month and thereby every 3months. The median patient age of the 55 patients included in this study was 69 (range: 51-90) years. BMD gradually increased in the lumbar spine and femoral neck and u-NTX levels were lowest at 3months post-initiation of therapy. Patients were divided into two groups based on the change ratio of u-NTX 3months post-denosumab administration. Of these, the group with higher change ratio showed a higher degree of BMD restoration in the lumbar spine and femoral neck 6months post-denosumab treatment. Denosumab increased BMD in patients treated with aromatase inhibitors. The u-NTX level decreased soon after start of denosumab treatment, and its change ratio is predictive of improvement in BMD.