Preservation Of Bone Mineral Density Research Articles

Influence of broach surface design of a fully hydroxyapatite coated, double tapered stem on periprosthetic bone mineral density after total hip arthroplasty: a study based on the morphology of the proximal femur.

This study aimed to compare the impact of different broach surface designs on post-operative clinical outcomes, bone reactions and changes in bone mineral density (BMD) in patients who underwent total hip arthroplasty (THA) using a fully hydroxyapatite coated and double tapered stem with either compaction shape (COM) or hybrid shape (HYB) broaches. A retrospective analysis was conducted on 76 patients (100 hips) who underwent primary THA using the Avenir complete stem®. Patients were divided into two groups: the COM broach group (50 hips) and HYB broach group (50 hips). We evaluated clinical outcomes using the Japanese Orthopaedic Association hip scores one month before the surgery, and 12 and 24months after the surgery. Radiographic findings, including stem alignment angles, radiolucent lines, spot welds, and cortical hypertrophy, were assessed. BMD around the stem in Gruen zones 1-7 was evaluated using dual-energy X-ray absorptiometry (DEXA) at 7days, 12, and 24months post-operatively. The Dorr classification was used to assess femoral morphology. There were no significant differences in clinical outcomes, radiographic findings, or BMD changes between the COM and HYB broach groups in the overall patient cohort. However, in Dorr type A femurs, the COM broach group demonstrated superior BMD superior preservation in zones 1 and 7 after 12months and in zones 1, 6 and 7 after 24months. Additionally, in Dorr type B femurs, significant BMD preservation was observed in zone 3 at 24months in the COM broach group. This study suggests that the broach surface design of fully hydroxyapatite coated stems may influence periprosthetic BMD changes, especially in Dorr type A and B femurs. Surgeons should consider broach selection based on patient-specific femoral morphology to optimize BMD preservation in THA procedures using fully hydroxyapatite coated stems.

Influence of broach surface design of a fully hydroxyapatite coated, double tapered stem on periprosthetic bone mineral density after total hip arthroplasty: a study based on the morphology of the proximal femur.

This study aimed to compare the impact of different broach surface designs on post-operative clinical outcomes, bone reactions and changes in bone mineral density (BMD) in patients who underwent total hip arthroplasty (THA) using a fully hydroxyapatite coated and double tapered stem with either compaction shape (COM) or hybrid shape (HYB) broaches. A retrospective analysis was conducted on 76 patients (100 hips) who underwent primary THA using the Avenir complete stem®. Patients were divided into two groups: the COM broach group (50 hips) and HYB broach group (50 hips). We evaluated clinical outcomes using the Japanese Orthopaedic Association hip scores one month before the surgery, and 12 and 24months after the surgery. Radiographic findings, including stem alignment angles, radiolucent lines, spot welds, and cortical hypertrophy, were assessed. BMD around the stem in Gruen zones 1-7 was evaluated using dual-energy X-ray absorptiometry (DEXA) at 7days, 12, and 24months post-operatively. The Dorr classification was used to assess femoral morphology. There were no significant differences in clinical outcomes, radiographic findings, or BMD changes between the COM and HYB broach groups in the overall patient cohort. However, in Dorr type A femurs, the COM broach group demonstrated superior BMD superior preservation in zones 1 and 7 after 12months and in zones 1, 6 and 7 after 24months. Additionally, in Dorr type B femurs, significant BMD preservation was observed in zone 3 at 24months in the COM broach group. This study suggests that the broach surface design of fully hydroxyapatite coated stems may influence periprosthetic BMD changes, especially in Dorr type A and B femurs. Surgeons should consider broach selection based on patient-specific femoral morphology to optimize BMD preservation in THA procedures using fully hydroxyapatite coated stems.

Obesity pharmacotherapy in older adults: a narrative review of evidence.

The prevalence of obesity in older adults (people aged >60 years) is increasing in line with the demographic shift in global populations. Despite knowledge of obesity-related complications in younger adults (increased risk of type 2 diabetes, liver and cardiovascular disease and malignancy), these considerations may be outweighed, in older adults, by concerns regarding weight-loss induced reduction in skeletal muscle and bone mass, and the awareness of the 'obesity paradox'. Obesity in the elderly contributes to various obesity-related complications from cardiometabolic disease and cancer, to functional decline, worsening cognition, and quality of life, that will have already suffered an age-related decline. Lifestyle interventions remain the cornerstone of obesity management in older adults, with emphasis on resistance training for muscle strength and bone mineral density preservation. However, in older adults with obesity refractory to lifestyle strategies, pharmacotherapy, using anti-obesity medicines (AOMs), can be a useful adjunct. Recent evidence suggests that intentional weight loss in older adults with overweight and obesity is effective and safe, hence a diminishing reluctance to use AOMs in this more vulnerable population. Despite nine AOMs being currently approved for the treatment of obesity, limited clinical trial evidence in older adults predominantly focuses on incretin therapy with glucagon-like peptide-1 receptor agonists (liraglutide, semaglutide, and tirzepatide). AOMs enhance weight loss and reduce cardiometabolic events, while maintaining muscle mass. Future randomised controlled trials should specifically evaluate the effectiveness of novel AOMs for long-term weight management in older adults with obesity, carefully considering the impact on body composition and functional ability, as well as health economics.

High content omega-3 fish oil co-treatment maintains proper bone physiology in glucocorticoid treated autoimmune mice

Despite the known side effects of glucocorticoid therapy, such as a higher risk of osteoporosis, fractures, and reduced bone density, it remains a frequently prescribed treatment for autoimmune disorders due to its strong anti-inflammatory and immunosuppressive properties. If strategies could be identified to reduce the side effects commonly associated with glucocorticoid use, it could lead to more frequent and safer use of this treatment option for autoimmune diseases. In this work, the combined effects of high content omega-3 fish oil (HCW3FO) and a synthetic glucocorticoid, methylprednisolone (MP) medication are investigated in relation to bone mineral density (BMD) reduction in arthritis prone female MRL-lpr/lpr mice. Two treatment groups were introduced to the mice when they were 4 months old: one group was given weekly injections of PBS, while the other group was given either 5 mg/kg MP or 20 mg/kg MP. Additionally, both groups were provided with the AIN93M diet, supplemented with either 4% corn oil or 4% HCW3FO daily, for a duration of 8 weeks. Prior to initiating the drug injections and dietary modifications, the mice underwent dual energy x-ray absorptiometry (DXA) scans to establish their baseline BMD values. To find out their ultimate BMD values, the mice underwent another DXA scan eight weeks later, right before being sacrificed. Over the course of eight weeks, the MP treatment did not lead to a significant reduction in BMD across various bone regions, except for the lumbar regions. Similarly, the HCW3FO treatment alone did not offer protection against BMD loss in MRL-lpr/lpr mice. However, when MP and HCW3FO were combined, it resulted in a remarkable preservation of BMD in different bone regions. This enhanced protection against BMD loss was associated with a reduced number of tartrate-resistant acid phosphatase (TRAP) positive areas and an increased number of alkaline phosphatase (ALP) positive areas in tibial sections as revealed by immunohistochemistry. Our findings provide compelling evidence that the combination of MP and HCW3FO maintains bone health in arthritis-prone MRL-lpr/lpr mice by promoting a balance between bone resorption and bone formation. Co-treatment with HCW3FO may hold promise as a potential strategy for preventing bone deterioration induced by long-term glucocorticoid therapy. Before moving on to clinical trials, more in vitro research into the mechanisms should be carried out alongside preclinical studies in mice with inflammatory diseases. QUCG-CAS-2122-2. 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.

Calcium-based phosphate binders and bone mineral density in patients undergoing hemodialysis: a retrospective cohort study.

Calcium supplements are commonly prescribed to prevent fractures in patients with osteoporosis. Nonetheless, they are generally eschewed in hemodialysis patients because they increase vascular calcification and induce cardiovascular disease. This retrospective cohort study aimed to investigate the effect of calcium-based phosphate binders (CBPB) on bone mineral density (BMD) in hemodialysis patients. Outpatients on dialysis who underwent BMD measurement from January to December 2017, whose data on BMD trends and CBPB administration were recorded over the next 4years, were enrolled. Patients receiving anti-osteoporotic medications were excluded. The association between the presence and duration of CBPB administration and changes in BMD was evaluated. The femoral neck's BMD decreased from 0.836g/cm2 (0.702-0.952) to 0.764g/cm2 (0.636-0.896) (P < 0.001) in the non-CBPB group (patients who never received CBPB over 4years, n = 32). The CBPB group (n = 56) exhibited only a minute decrease from 0.833g/cm2 (0.736-0.965) to 0.824g/cm2 (0.706-0.939) (P = 0.004). Multivariate linear regression analysis revealed better BMD maintenance in the CBPB group [β-coefficient (95% CI): 0.033 (0.001-0.065); P = 0.046] than in the non-CBPB group. Additionally, the prolonged-CBPB administration group showed superior BMD preservation [β-coefficient (95% CI): 0.038 (0.001-0.076); P = 0.042]. CBPB administration may be associated with BMD maintenance.

Bone indices and body weight changes of ovariectomized rats treated with&lt;i&gt; Marantodes pumilum&lt;/i&gt; var. &lt;i&gt;Alata&lt;/i&gt;

Marantodes pumilim var. alata (MPva) is a popular female aphrodisiac and known source of phytoestrogens. It is traditionally used to manage postmenopausal crisis and preserve bone health in women. The study aims to investigate the effects of MPva on bone indices and bodyweight of post-menopausal rats. Thirty female Sprague-Dawley rats were divided into groups (n=6): Healthy control (Sham); ovariectomized control (OVXC); Estrogen treatment (ERT); plant leaf extract treatment (MPr) and plant root extract treatment (MPv) groups. All rats (except the Sham-operated group) were ovariectomized. After 2-weeks healing period, the ERT group was treated with 64.5 μg/kg estrogen while MPv and MPr groups received pre-determined optimal daily dose of MPva leaf and root extracts, respectively. Changes in bodyweight of rats were monitored through an eight-weeks treatment period after which rats were euthanized for testing of bone parameters. Both leaves and roots of MPva (20 mg/kg) were found to show optimal preservation of bone mineral density and mechanical strength. Untreated estrogen-deficient rats (OVXC) showed significant weight-gain when compared with the healthy control (Sham) (p&lt;0.05). Treatment with MPva leaf and root extracts, similar to treatment with estrogen, significantly suppressed weight-gain observed in the estrogen-deficient (OVXC) group (p&lt;0.05). In conclusion, treatment with MPva leaf and root extracts preserved bone strength. In addition, it suppressed weight gain in postmenopausal rats, an outcome that makes MPva more beneficial to postmenopausal women that may experience weight gain.

Ectopic fat in muscle and poor glycemic control are negatively associated with trabecular bone score in type 2 diabetes

IntroductionType 2 Diabetes (T2D) is associated with fractures, despite preserved Bone Mineral Density (BMD). This study aimed to evaluate the relationship between BMD and trabecular bone score (TBS) with the reallocation of fat within muscle in individuals with eutrophy, obesity, and T2D. MethodsThe subjects were divided into three groups: eutrophic controls paired by age and sex with the T2D group (n = 23), controls diagnosed with obesity paired by age, sex, and body mass index with the T2D group (n = 27), and the T2D group (n = 29). BMD and body fat percentage were determined using dual-energy X-Ray absorptiometry. TBS was determined using TBS iNsight software. Intra and extramyocellular lipids in the soleus were measured using proton magnetic resonance spectroscopy. ResultsTBS was lower in the T2D group than in the other two groups. Glycated hemoglobin (A1c) was negatively associated with TBS. Body fat percentage was negatively associated with TBS and Total Hip (TH) BMD. TH BMD was positively associated with intramuscular lipids. A trend of negative association was observed between intramuscular lipids and TBS. ConclusionThis study showed for the first time that the reallocation of lipids within muscle has a negative association with TBS. Moreover, these results are consistent with previous studies showing a negative association between a parameter related to insulin resistance (intramuscular lipids) and TBS.

Design of an Observational Study (PROVE) to Assess the Long-Term Effects of Prophylaxis with Simoctocog Alfa or Emicizumab on Joint and Bone Health in Hemophilia a Patients

Background: Arthropathy caused by repeated joint bleeding is a major complication in patients with severe hemophilia A and is associated with long-term morbidity. Factor VIII (FVIII) prophylaxis has proven benefits for prevention of bleeding, including joint bleeding, in these patients. Alongside preservation of joint health, FVIII prophylaxis may preserve bone mineral density (BMD) and reduce the risk of fractures. Emicizumab is a bi-specific monoclonal antibody with no structural homology to FVIII and is approved for prophylaxis in hemophilia A patients. However, data on the long-term impact of emicizumab on joint and bone health are limited. Aims: To assess the impact of long-term prophylaxis with simoctocog alfa (Nuwiq ®; a fourth generation recombinant FVIII) versus emicizumab on joint and bone health in people with hemophilia A. Methods: PROVE is a multinational, prospective, two-arm, low-interventional study that will collect clinical data on joint and bone health in patients receiving prophylaxis with simoctocog alfa or emicizumab in routine clinical practice. Approximately 200 male participants (100 in each treatment arm) at least 12 years of age with severe hemophilia A (FVIII activity [FVIII:C] &amp;lt;1%) will be enrolled. Written, informed consent will be obtained from each patient or their legal representative. The primary objective of the study is to evaluate the long-term effect of simoctocog alfa versus emicizumab on joint health as measured by magnetic resonance imaging (MRI). The primary endpoint will be a between-group comparison of the change in total score on the extended MRI (eMRI) scale (Table 1). Secondary and exploratory endpoints include the impact of simoctocog alfa vs emicizumab on bleeding rates, joint and bone health, physical activity, quality of life and safety (Table 1). Study treatments will be defined by the treating physician prior to inclusion of a patient into the study. Patients will not be randomized to the treatment groups but will continue with their current prophylactic regimen (simoctocog alfa or emicizumab). Patients will be provided with an electronic diary (eDiary) in which to record study related data, including treatment-related data, bleeding event details, fracture details, concomitant medications and adverse drug reactions. Each patient will be followed for up to 4 years. An interim analysis is planned after 2 years. Conclusion: ThePROVE study aims to generate real-world data on the long-term effects of prophylaxis with simoctocog alfa or emicizumab on joint and bone health in hemophilia A.

THU413 Does Continuous Positive Airway Pressure Affect Bone Loss Process In The Population Of Sleep Apnea?

Abstract Disclosure: Y. Chen: None. A. Suresh: None. S. Haile: None. Z. Perciuleac: None. B. Soni: None. A. Cuevas Velazquez: None. A. Amirian: None. C. Udeh: None. L. Sangha: None. B. Ravichander: None. K. Aljassani: None. R. Joshi: None. A. Atrash: None. N. Ramesh: None. J. Sta. Cruz: None. S. Al-saadi: None. Introduction: Patients with obstructive sleep apnea (OSA) were reported to have higher risk of developing osteoporosis or increased bone loss. One of the theories suggested nocturnal hypoxia led to imbalanced osteoclastic activity and contributed to bone loss. Continuous Positive Airway Pressure (CPAP) is the first-line treatment for OSA, which improves airway obstruction and limits hypoxia. This study attempts to evaluate if compliant with CPAP therapy reduces bone loss. Methods: This retrospective study included patients who visited UPMC Central Pa. sleep medicine clinic from January 2010 to October 2022 with diagnosis of OSA and have at least two dual-energy X-ray absorptiometry (DEXA) after the OSA diagnosis. Patients’ records of CPAP usage on two databases, Respironics and Resmed, were used to assess the compliance of the therapy. The definition of compliance is average usage of 4hrs/night; frequency of use being 70% or above. Patient demographics, CPAP compliance, bone mineral density (BMD) and T-scores of two DEXAs were obtained. All data after diagnosis of active malignancy, hyperparathyroidism, end stage renal disease, or after patient received osteoporosis pharmacological treatment are excluded. Annual change of BMD was calculated with the difference of BMD between the two DEXA scans divided by the study interval. Two-sample t-test and chi-square test were used for analysis. Results: 265 patients were included for analysis, with 254 female (95.8%), 92.1% Caucasian, mean age 68.3 years old, mean BMI 36.7kg/m2. 165 patients were compliant and 100 were non-compliant. The two groups were identical on demographic data including age, sex, ethnicities. The median of annual BMD changes at L-spine, left femur neck, left femur total, and left radius were 0.003, −0.003, −0.002, −0.002 g/cm2 respectively in compliant group and 0.003, 0, −0.006, −0.002 g/ cm2 in non-compliant group. The annual changes of T-scores were 0, −0.043, 0, −0.036 for the compliant group and 0, 0, −0.051, −0.034 for non-compliant group. No significant within-group or between-group difference in annual bone density reduction on BMD or T-score was noted in our analysis. Discussions: Our study did not reveal the benefit of treating OSA on bone loss. Small sample size could be the leading factor for the limited effect size. Retrospective study design also restricted our study population to predominantly postmenopausal Caucasian female. Further adjustments for possible confounding factors including BMI and age might be beneficial. Future study with prospective design, larger sample size, and diverse population is encouraged to discover the effect of CPAP therapy on BMD preservation. Presentation: Thursday, June 15, 2023

LIBERTY randomized withdrawal study: relugolix combination therapy for heavy menstrual bleeding associated with uterine fibroids

In the pivotal LIBERTY 1 and 2 trials and long-term extension study, once-daily relugolix combination therapy (40 mg relugolix, 1 mg estradiol, 0.5 mg norethindrone acetate) reduced menstrual blood loss volume and pain among women with uterine fibroids. Relugolix combination therapy was well tolerated with preservation of bone mineral density through 52 weeks. This study aimed to report the 2-year relugolix combination therapy efficacy and safety results of the phase 3 LIBERTY randomized withdrawal study. Women with uterine fibroid-associated heavy menstrual bleeding who completed the 24-week LIBERTY 1 or 2 trials, followed by the 28-week long-term extension study (up to 52 weeks total treatment), and who met the responder criteria (menstrual blood loss volume <80 mL and ≥50% reduction from pivotal study baseline at week 48 [week 24 of long-term extension]) were randomized in a 1:1 ratio to either blinded treatment with relugolix combination therapy or placebo for 52 weeks (total treatment period, 104 weeks). For women who had a relapse of heavy menstrual bleeding during the study (menstrual blood loss volume ≥80 mL), open-label relugolix combination therapy was offered. The primary endpoint was the proportion of women who maintained menstrual blood loss volume <80 mL through week 76 (week 24 of randomized withdrawal study). Secondary endpoints included time to menstrual blood loss volume ≥80 mL, proportion of women who maintained a menstrual blood loss volume of <80 mL through week 104 (over the 52-week randomized treatment period), the proportion of women who achieved or maintained amenorrhea at week 76 at the end of treatment, and the change in Uterine Fibroid Symptom-Quality of Life Bleeding and Pelvic Discomfort Scale and symptom severity scores. Analyses were performed for the modified intent-to-treat population, including all randomized women who received ≥1 dose of the study drug. Of the 229 randomized women (relugolix combination therapy, n=115; placebo, n=114), 228 received the study drug and 175 (76.7%) completed the randomized withdrawal study. Through week 76, 78.4% of women on relugolix combination therapy maintained menstrual blood loss volume <80 mL vs 15.1% in the placebo group (difference, 63.4%; 95% confidence interval, 52.9%-73.9%; P<.0001). At week 104, 69.8% of women on relugolix combination therapy maintained menstrual blood loss volume <80 mL vs 11.8% in the placebo group (difference, 58.0%; 95% confidence interval, 47.0%-69.1%; P<.0001). Through week 104, 88.3% of women on placebo relapsed with heavy menstrual bleeding (median time to relapse, 5.9 weeks). Among the 89 women in the placebo group who relapsed and received open-label rescue treatment, 87 women responded to relugolix combination therapy with a menstrual blood loss volume <80 mL. The proportion of women who achieved or maintained amenorrhea were 57.4% vs 13.3% at week 76 (difference, 44.1%; 95% confidence interval, 33.10%-55.1%; P<.0001) and 58.3% vs 10.6% at week 104 (difference, 47.6%; 95% confidence interval, 37.0%-58.3%; nominal P<.0001) for relugolix combination therapy and the placebo group, respectively. Relugolix combination therapy was generally well tolerated; no new safety signals were identified, and the adverse event profile over the second year was consistent with that reported through the first year of treatment. Bone mineral density remained stable in women who received relugolix combination therapy from week 52 to week 104. In women continuously treated with relugolix combination therapy up to 2 years, bone mineral density was generally preserved. After 2 years of treatment with relugolix combination therapy, there was evidence of durability of the effect in maintaining low menstrual blood loss volume in women with symptomatic uterine fibroids. Most women had return of heavy menstrual bleeding and associated symptoms after treatment cessation, which improved upon retreatment with relugolix combination therapy. Relugolix combination therapy was well tolerated, the adverse event profile remained consistent, and the mean bone mineral density was generally preserved through 2 years of treatment.

Rectangular tapered short stem excellently preserves proximal bone mineral density preservation than tapered wedge short stem

Fitmore stem is a rectangular, tapered, short, cementless stem. A characteristic feature of this stem is that it provides rotational stability due to the high medullary occupancy achieved by its rectangular cross-section and thick antero- posterior width. We aimed to investigate the differences in periprosthetic bone remodelling between a rectangular- tapered short stem and a short tapered-wedge stem. Eighty patients who underwent primary total hip arthroplasty using a rectangular-tapered short stem (Fitmore) or a short tapered-wedge stem (Tri-Lock BPS) were enrolled in this study. Bone mineral densities (BMDs) in the seven Gruen zones were evaluated using dual-energy X-ray absorptiometry at baseline, and at 6 and 24 months postoperatively. Peri-prosthetic BMD and clinical factors were assessed and compared. In addition, correlations between periprosthetic BMD changes and stem anteversion error were analyzed using Pearson’s correlation coefficient in the two groups. A significantly better postoperative periprosthetic BMD change was found in zones 1 and 7 in the rectangular-tapered group. Additionally, no significant correlation was observed between stem anteversion error and periprosthetic BMD changes in the rectangular-tapered groups. However, in the tapered-wedge group, there were significant negative correlations between the stem anteversion error and BMD changes at 6 months and 24 months in zones 1 and 7. In the rectangular-tapered group, a significantly better postoperative periprosthetic BMD change was found particularly in the region proximal to the stem. Rectangular-tapered short stem can be more resistant to rotation due to higher medullary occupancy and may lead to better periprosthetic BMD than the tapered-wedge short stem, especially in the proximal region of the stem.

EVALUATION OF PROXIMAL FEMORAL BONE MINERAL DENSITY IN CEMENTLESS TOTAL HIP ARTHROPLASTY: A THREE-ARM PROSPECTIVE RANDOMIZED CONTROLLED TRIAL

Femoral stem design affects periprosthetic bone mineral density (BMD), which may impact long term survival of cementless implants in total hip arthroplasty (THA). The aim of this study was to examine proximal femoral BMD in three morphologically different uncemented femoral stems designs to investigate whether one particular design resulted in improved preservation of BMD.119 patients were randomized to receive either a proximally coated dual taper wedge stem, a proximally coated anatomic stem or a fully coated collarless triple tapered stem. Dual energy x-ray absorptiometry scans (Lunar iDXA, GE Healthcare, Madison, WI) assessed BMD across the seven Gruen zones pre-operatively, and post-operatively at 6-weeks, 1-year, and 2-years comparing the unoperated contralateral femur as a control.BMD increased in zones one (2.5%), two (17.1%), three (13.0%), five (10%) and six (17.9%) for all stems. Greater preservation of BMD was measured on the lateral cortex (zone 2) for both the dual taper wedge and anatomic stems (p = 0.019). The dual taper wedge stem also demonstrated preservation of BMD in the medial calcar (zone 7) whilst the anatomic and triple taper stem declined in this region, however this was not statistically significant (p = 0.059). BMD decreased on average by 2.1% in the mid-diaphysis region, distal to the stem tip (zone 4) for all implants. All stems performed equivalently at final follow-up in all patient reported outcome measures.Implant design was shown to impact BMD changes. All stems preserved bone at the metaphyseal level in early follow-up, which theoretically indicates favorable implant fixation. There was no significant stress shielding observed, however longer follow-up is required to elucidate the impact of this finding on implant survivorship.

O-191 Effects of relugolix combination therapy (Relugolix-CT) on uterine fibroid (UF) and uterine volume through 52 weeks: post hoc analysis of the LIBERTY Long-Term Extension study

Abstract Study question How does baseline UF and uterine volume impact the proportion of women achieving meaningful UF and uterine volume reductions with Relugolix-CT through 52 weeks? Summary answer Women with larger UF and uterine volumes at baseline may be more likely to experience clinically meaningful reductions of UF and uterine volume with Relugolix-CT. What is known already In the randomised, Phase 3 LIBERTY 1 and 2 pivotal studies, the efficacy and safety of once-daily Relugolix-CT (relugolix 40 mg, estradiol 1 mg, norethisterone acetate 0.5 mg) were demonstrated in premenopausal women (aged 18–50 years), with a significant reduction in UF-associated heavy menstrual bleeding (HMB) vs placebo, and preserved bone mineral density (BMD) through 24 weeks. The open-label, 28-week LIBERTY Long-Term Extension (LTE) study continued to demonstrate sustained menstrual blood loss reductions and preservation of BMD, alongside reductions in UF and uterine volume. Study design, size, duration The LIBERTY 1 and 2 studies of Relugolix-CT were conducted in 770 premenopausal women with UF-associated HMB. Women were randomised 1:1:1 to receive Relugolix-CT or placebo for 24 weeks, or delayed Relugolix-CT (relugolix 40 mg alone for 12 weeks, then Relugolix-CT for 12 weeks). Women who completed the pivotal trials were eligible to participate in the LIBERTY LTE study, receiving open-label Relugolix-CT for an additional 28 weeks. Participants/materials, setting, methods Endpoints of the LTE included change from baseline to Week 52 in UF and uterine volume. This post hoc analysis assessed the proportion of women who experienced a clinically meaningful reduction in UF or uterine volume of &amp;gt; 25% or &amp;gt; 50% through 52 weeks of Relugolix-CT. Subgroup analyses were performed to descriptively summarise the impact of UF and uterine volume at baseline (&amp;lt;25cm3 or ≥ 25cm3; &amp;lt;300cm3 or ≥ 300cm3, respectively) on change in UF and uterine volume. Main results and the role of chance In total, 477 women enrolled in the LTE, 363 completed 52 weeks of treatment, and 163 received Relugolix-CT continuously up to 52 weeks. At baseline, the mean (standard deviation) volume of the largest UF was 80.0 (145.1) cm3; mean (SD) uterine volume was 386.7 (320.5) cm3 in the Relugolix-CT group. At Week 24, 52.6% and 30.3% of women in the Relugolix-CT group experienced &amp;gt;25% and &amp;gt;50% reduction in UF volume, respectively. These proportions increased to 61.1% and 36.6%, respectively, at Week 52. For uterine volume, 36.1% and 4.5% experienced a &amp;gt; 25% and &amp;gt;50% reduction at Week 24, increasing to 41.2% and 9.6% at Week 52. At Week 52, of 81 women with a baseline UF volume of &amp;lt; 25cm3, 52.4% and 27.0% experienced a &amp;gt; 25% and &amp;gt;50% reduction in UF volume, respectively; 69.1% and 45.6% of 81 women with a baseline UF volume of ≥ 25cm3 experienced &amp;gt;25% and &amp;gt;50% reductions in UF volume, respectively. At Week 52, of 96 women with a baseline uterine volume of &amp;lt; 300cm3, 38.5% and 6.4% experienced a &amp;gt; 25% and &amp;gt;50% reduction in uterine volume; 44.8% and 13.8% of 67 women with a baseline uterine volume of ≥ 300cm3 experienced &amp;gt;25% and &amp;gt;50% reductions in uterine volume. Limitations, reasons for caution The study was conducted as an open-label study without a control group over the 28 weeks of the extension period. The present data are from a post hoc analysis of LIBERTY data without predefined criteria. Wider implications of the findings Treatment with Relugolix-CT led to a substantial reduction of UF and uterine volume in a large proportion of women with UF-associated HMB. Women with larger UF and uterine volume at baseline may be more likely to experience substantial reductions of UF and uterine volume. Trial registration number NCT03049735, NCT03103087, NCT03412890

Associations of Type 2 Diabetes, Body Composition, and Insulin Resistance with Bone Parameters: The Dubbo Osteoporosis Epidemiology Study.

Type 2 diabetes (T2D) may be associated with increased risk of fractures, despite preserved bone mineral density (BMD). Obesity and insulin resistance (IR) may have separate effects on bone turnover and bone strength, which contribute to skeletal fragility. We characterized and assessed the relative associations of obesity, body composition, IR, and T2D on bone turnover markers (BTMs), BMD, and advanced hip analysis (AHA). In this cross-sectional analysis of Dubbo Osteoporosis Epidemiology Study, 525 (61.3% women) participants were grouped according to T2D, IR (homeostasis model assessment insulin resistance [HOMA-IR] </≥2.5), and BMI (</≥25 kg/m2): insulin-sensitive lean (IS-L), insulin-sensitive overweight/obese (IS-O), insulin-resistant (IR), and T2D. BMD, AHA, and body composition, including visceral adipose tissue (VAT) (on dual-energy x-ray absorptiometry scan) and fasting BTMs, were assessed. Analyses performed using Bayesian model averaging and principal component analysis. T2D was associated with low BTMs (by 26%-30% [95% confidence interval [CI] 11%-46%] in women, 35% [95% CI 18%-48%] in men compared to IS-L), which persisted after adjustment for VAT. BTMs were similar among IR/IS-O/IS-L. BMD was similar among T2D/IR/IS-O; BMD was low only in IS-L. All groups were similar after adjustment for BMI. Similarly, AHA components were lowest in IS-L (attenuated following adjustment). On multivariate analysis, T2D was independently associated with BTMs. IR was also associated with C-terminal telopeptide of type 1 collagen in men. Age and body size were the strongest independent contributors to BMD and AHA. VAT was inversely associated with section modulus, cross-sectional area, cross-sectional moment of inertia in women, and hip axis length in men. Low bone turnover is associated with T2D and IR (in men), while BMD and hip strength/geometry are predominantly associated with body size. VAT, indicative of dysglycemia, is also associated with impaired bone geometry. Establishing the role of BTMs and AHA fracture risk may improve skeletal assessment in T2D people. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Bisphosphonates Preserve Bone Mineral Density and Suppress Bone Turnover Markers in Early Menopausal Women: A Systematic Review and Meta-Analysis of Randomized Trials.

Most women do not qualify for pharmacologic osteoporosis treatment until more than a decade after menopause, by which time they will have lost up to 30% of their bone mass and may have already sustained fractures. Short or intermittent courses of bisphosphonate therapy, initiated around the time of menopause, might prevent excessive bone loss and lower long-term fracture risk. We undertook a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the effects of nitrogen-containing bisphosphonates on fracture incidence, bone mineral density (BMD), and bone turnover markers in early menopausal women (ie, perimenopausal or <5 years postmenopausal) over ≥12 months. Medline, Embase, CENTRAL, and CINAHL were searched in July 2022. Risk of bias was evaluated using the Cochrane Risk of Bias 2 tool. Random effect meta-analysis was undertaken using RevMan v5.3. In total, 12 trials were included (n = 1722 women); five evaluated alendronate, three risedronate, three ibandronate, and one zoledronate. Four were at low risk of bias; eight raised some concerns. Fractures were infrequent in the three studies that reported them. Compared with placebo, bisphosphonates improved BMD over 12 months (mean percentage difference, 95% confidence interval [CI]) at the spine (4.32%, 95% CI, 3.10%-5.54%, p < 0.0001, n = 8 studies), the femoral neck (2.56%, 95% CI, 1.85%-3.27%, p = 0.001, n = 6 studies), and the total hip (1.22%, 95% CI 0.16%-2.28%, p = 0.002, n = 4 studies). Over treatment durations of 24 to 72 months, bisphosphonates improved BMD at the spine (5.81%, 95% CI 4.71%-6.91%, p < 0.0001, n = 8 studies), femoral neck (3.89%, 95% CI 2.73%-5.05%, p = 0.0001, n = 5 studies) and total hip (4.09%, 95% CI 2.81%-5.37%, p < 0.0001, n = 4 studies). Bisphosphonates reduced urinary N-telopeptide (-52.2%, 95% CI -60.3% to -44.2%, p < 0.00001, n = 3 studies) and bone-specific alkaline phosphatase (-34.2%, 95% CI -42.6% to -25.8%, p < 0.00001, n = 4 studies) more than placebo at 12 months. This systematic review and meta-analysis shows that bisphosphonates improve BMD and lower bone turnover markers in early menopause, warranting further investigation of these agents for osteoporosis prevention. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Dried Fruits: Bioactives, Effects on Gut Microbiota, and Possible Health Benefits—An Update

Dried fruits contain many bioactive compounds broadly classified as phytochemicals including phenolics, flavonoids, carotenoids, proanthocyanidins, stilbenes, chalcones/dihydrochalcones, and phytoestrogens. These compounds have antioxidant effects that may benefit health. Dried fruits are also a diverse group of foods with varying fibre contents. The evaluation of the biological activity of these bioactive compounds, including their bioaccessibility and bioavailability, may contribute to the understanding of the health effects of dried fruits. Limited evidence suggests that dried fruits (raisins, cranberries, dates, and prunes) affect human gut microbiota composition in a potentially beneficial manner (in terms of effects on Bifidobacteria, Faecalibacterium prausnitzii, Lactobacillus, Ruminococcaceae, Klebsiella spp., and Prevotella spp.). There is little epidemiological evidence about the association of dried fruit consumption with cardiovascular disease incidence and mortality, as well as the risk of type 2 diabetes or obesity. Clinical trial evidence for the effects of dried fruit consumption on cardiovascular risk factors, including glycaemic control, is mixed. Clinical trial evidence suggests prunes might preserve bone mineral density in postmenopausal women. Consumption of dried fruits is associated with higher-quality diets. Studies are needed to increase our understanding of the health effects of dried fruits and the underlying biological mechanisms.

Leisure time physical activity and bone mineral density preservation during the menopause transition and postmenopause: a longitudinal cohort analysis from the Study of Women's Health Across the Nation (SWAN)

Whether greater leisure time physical activity (LTPA) is associated with less bone mineral density (BMD) loss during the menopause transition (MT) remains an open question. We hypothesized that: 1) larger increases in LTPA from pre-/early perimenopause (period 1) to late perimenopause/postmenopause (period 2) would be associated with a slower period 2 BMD loss rate; and 2) greater entire-study LTPA levels would be associated with better final absolute BMD (g/cm2). Data were from of the Study of Women's Health Across the Nation (1996-2017). Exclusions were: bone beneficial medications, inability to identify start of the MT, and extreme BMD change rates. LTPA measures were a validated ordinal scale and number of metabolic equivalents per hour per week (MET hr wk-1) from sport/exercise. Multiply adjusted, linear regression models estimated: 1) BMD decline rate (annualized %) as a function of LTPA change; and 2) final BMD as a function of entire-study LTPA. Median [p25, p75] MET hr wk-1 were 4.2 [0.9, 10.1] and 4.9 [1.4, 11.2] in periods 1 and 2, respectively; walking was the commonest activity. In adjusted models (N=875), greater increases in LTPA ordinal score and MET hr wk-1 were statistically significantly associated with a slower decline in femoral neck (FN) BMD. Larger entire-study averages of each LTPA measure were statistically significantly related to better final FN and lumbar spine BMD levels. Findings suggest that LTPA, at modest levels, mitigate MT-related BMD decline and even small increases in intensity, duration or frequency of common activities may lessen bone loss at the population level. US-NIH.

Use of oral GnRH antagonists combined therapy in the management of symptomatic uterine fibroids.

Uterine fibroids have an impact on women's lives due to their high prevalence, physical symptoms, their consequences on patients' emotional and psychological well-being and loss of work productivity. The choice of therapeutical approaches varies depending on several factors, and therefore should be applied individually. Currently, there is an unmet need for good, reliable, uterine-sparing options. The oral GnRH antagonists (Elagolix, Relugolix, Linzagolix) represent a new alternative for the medical management of hormone-dependent gynaecological diseases such as uterine fibroids or endometriosis. They rapidly bind to the GnRH receptor, block endogenous GnRH activity and directly suppress LH and FSH production, avoiding unwanted flare-up effects. Some GnRH antagonists are marketed in combination with hormone replacement therapy add-back to counteract hypo-oestrogenic side effects. According to the registration trials, once-daily GhRH antagonist combination therapy results in a significant reduction in menstrual bleeding, as compared with placebo, and preserves bone mineral density, for up to 104 weeks. Further studies in the long term are needed to evaluate the whole impact of medical treatment of uterine fibroids on the management of this common women's disease.

Disease-Modifying Adjunctive Therapy of Osteopenia and Osteoporosis with a Multimineral Marine Extract, LithoLexal® Bone

There is evidence to suggest that restoration of major/rare biominerals by supplementation can produce osteogenic and anti-resorptive effects in humans. LithoLexal® is a natural extract harvested from a marine alga, Lithothamnion sp., with a porous microstructure and multimolecular composition rich in calcium (32% w/w) and magnesium (2.2% w/w) together with ~72 trace bioelements. In vitro, LithoLexal® demonstrated cellular-level osteogenic efficacy through enhancing the maturation and activity of pre-osteoblasts. This extract also expressed the ability to suppress osteoclastogenesis by downregulating the pro-resorptive cytokines TNF-α and IL-1β and the master regulator of inflammation NF-κB. Parathyroid hormone inhibition of parathyroid hormone secretion is another bioactivity of LithoLexal® Bone reported with both short- and long-term administration at a longer duration and higher magnitude than what calcium carbonate could induce. Due to these bioactivities that affect pathogenetic factors of osteoporosis, LithoLexal® Bone is referred to as a disease-modifying adjunctive therapy (DMAT). In postmenopausal animal models, LithoLexal® monotherapy preserved bone mineral density, microarchitecture, and biomechanical properties, while calcium carbonate failed to produce significant outcomes. The pro-resorptive effect of a high-fat diet was also efficiently counteracted in vivo by supplementary LithoLexal®. A large clinical trial on postmenopausal women verified the mitigating effects of LithoLexal® Bone on bone resorption and turnover rate. The characteristic composition of LithoLexal® together with its lattice microstructure are suggested to underlie its in vivo bioactivities. In conclusion, adjunctive therapy with LithoLexal® Bone is an attractive option for clinical prevention and treatment of osteopenia/osteoporosis.

EVALUATION OF PROXIMAL FEMORAL BONE MINERAL DENSITY IN CEMENTLESS TOTAL HIP ARTHROPLASTY: A THREE-ARM PROSPECTIVE RANDOMIZED CONTROL TRIAL

Femoral stem design affects periprosthetic bone mineral density (BMD), which may impact long term survival of cementless implants in total hip arthroplasty (THA). The aim of this study was to examine proximal femoral BMD in three morphologically different uncemented femoral stems designs to investigate whether one particular design resulted in improved preservation of BMDMethods: 119 patients were randomised to receive either a proximally coated dual taper wedge stem, a proximally coated anatomic stem or a fully coated collarless triple tapered stem. All surgeries were performed via the posterior approach with mobilization on the day of surgery. Dual energy x-ray absorptiometry scans (Lunar iDXA, GE Healthcare, Madison, WI) assessed BMD across the seven Gruen zones pre-operatively, and post-operatively at 6-weeks, 1-year, and 2-years and compared to the unoperated contralateral femur as a control. Patient reported outcome measures of pain, function and health were also included at these corresponding follow-ups.BMD increased in zones one (2.5%), two (17.1%), three (13.0%), five (10%) and six (17.9%) for all stems. Greater preservation of BMD was measured on the lateral cortex (zone 2) for both the dual taper wedge and anatomic stems (p = 0.019). The dual taper wedge stem also demonstrated preservation of BMD in the medial calcar (zone 7) whilst the anatomic and triple taper stem declined in this region, however this was not statistically significant (p = 0.059). BMD decreased on average by 2.1% inthe mid-diaphysis region, distal to the stem tip (zone 4) for all implants. All stems performed equivalently at final follow-up in all patient reported outcome measures.This study demonstrated maintenance of femoral BMD in three different cementless femoral stem designs, with all achieving excellent improvements in patient reported outcomes. There was no significant stress shielding observed, however longer follow-up is required to elucidate the impact of this finding on implant survivorship.