Significant Change In Bone Mineral Density Research Articles

Clinical experience with denosumab discontinuation.

Discontinuing denosumab (DMAb) rapidly decreases bone mineral density (BMD) and increases the risk of multiple vertebral fractures. We wanted to examine if the recommendation stated in the ECTS position paper on DMAb discontinuation can prevent the bone loss in a clinical setting. We conducted a retrospective cohort study based on medical records of patients referred for DMAb discontinuation. We administered zoledronate (ZOL) 6 months after the last DMAb injection and 3, 6, 12, and 24 months thereafter if p-C-terminal collagen crosslinks (CTX) increased above 0.5 μg/l or BMD decreased (≥ 5% at the hip, ≥ 3% at the spine) at months 12 and 24. We included 66 women and men discontinuing DMAb after a mean treatment duration of 6.7 ± 2.7 (mean ± SD) years. BMD decreased 12 months after the initial ZOL treatment by 2.5 ± 4.2% and 1.9 ± 2.5% at the LS and TH, respectively (n = 44) (p ≤ 0.001 for all). There was no significant change in FNBMD (0.0 ± 5.1) (p > 0.05). No significant change in BMD was seen from month 12 to month 24 at any site (p > 0.05 for all). Thirty percent and twenty-two percent of patients experienced flu-like symptoms after the first and second ZOL infusion. No fractures occurred during the study period. Adhering to the recommendation in the ECTS position statement, a mean of 3 infusions of ZOL limited the bone loss 12 and 24 months after DMAb discontinuation, thereby preserving most of the BMD gained during DMAb treatment. The frequent occurrence of flu-like symptoms after ZOL proves to be a challenge, showing that routine prophylaxis against acute phase responses should be considered in patients treated with ZOL after discontinuing DMAb.

Effects of Dual-Release Hydrocortisone on Bone Metabolism in Primary and Secondary Adrenal Insufficiency: A 6-Year Study.

Patients with primary (PAI) and secondary adrenal insufficiency (SAI) experience bone metabolism alterations, possibly due to excessive replacement. Dual-release hydrocortisone (DR-HC) has shown promising effects on several parameters, but bone metabolism has seldom been investigated. We evaluated the long-term effects of once-daily DR-HC on bone in PAI and SAI. Patients on immediate-release glucocorticoid therapy were evaluated before and up to 6 years (range, 4-6) after switching to equivalent doses of DR-HC, yielding data on bone turnover markers, femoral and lumbar spine bone mineral density (BMD), and trabecular bone score (TBS). Thirty-two patients (19 PAI, 18 female), median age 52 years (39.4-60.7), were included. At baseline, osteopenia was observed in 38% of patients and osteoporosis in 9%, while TBS was at least partially degraded in 41.4%. Higher body surface area-adjusted glucocorticoid doses predicted worse neck (P < .001) and total hip BMD (P < .001). Longitudinal analysis showed no significant change in BMD. TBS showed a trend toward decrease (P = .090). Bone markers were stable, albeit osteocalcin levels significantly varied. PAI and SAI subgroups behaved similarly, as did patients switching from hydrocortisone or cortisone acetate. Compared with men, women exhibited worse decline in TBS (P = .017) and a similar trend for neck BMD (P = .053). After 6 years of chronic DR-HC replacement, BMD and bone markers remained stable. TBS decline is more likely due to an age-related derangement of bone microarchitecture rather than a glucocorticoid effect. Our data confirm the safety of DR-HC replacement on bone health in both PAI and SAI patients.

The Effect of Zonisamide on Rat Bone Mass, Structure, and Metabolism

Introduction: Our study aimed to investigate the effect of zonisamide (ZNS) on bone metabolism in the rat model. Methods: Eight-week-old rats were divided into four groups. The sham-operated control group (SHAM) and the control group after orchidectomy (ORX) received the standard laboratory diet (SLD). The experimental group after orchidectomy (ORX+ZNS) and the sham-operated control group (SHAM+ZNS) received SLD enriched with ZNS for 12 weeks. Bone marker concentrations in serum of receptor activator of nuclear factor kappa B ligand, PINP, and osteoprotegerin, and the levels of sclerostin and bone alkaline phosphatase in bone homogenate, were measured using an enzyme-linked immunosorbent assay. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. The femurs were used for biomechanical testing. Results: We found a statistically significant reduction in BMD and biomechanical strength 12 weeks after orchidectomy of the rats (ORX). After ZNS administration to orchidectomized rats (ORX+ZNS) and the sham-operated control rats (SHAM+ZNS), there were no statistically significant changes in BMD, bone turnover markers, or biomechanical properties as compared with the ORX group and SHAM group. Conclusions: The results suggest that administration of ZNS to rats exerts no negative effect on BMD, bone metabolism markers, or biomechanical properties.

A 2-Year Longitudinal Study of Bone Mineral Density in Collegiate Distance Runners.

Brimacomb, OE, Martinez, MP, McCormack, WP, and Almstedt, HC. A 2-year longitudinal study of bone mineral density in collegiate distance runners. J Strength Cond Res 37(8): 1654-1659, 2023-The purpose of this investigation was to examine changes in bone mineral density (BMD) of male and female collegiate distance runners over 2 years. Bone mineral density of 29 collegiate distance runners (16 men and 13 women) were measured 5 times over 24 months using dual-energy x-ray absorptiometry (DXA) at the anterior-posterior (AP) and lateral (LAT) spine, femoral neck (FN), total hip (TH), whole body (WB), and ultradistal (UD) forearm. Repeated-measures multivariate analysis of covariance, with bone-free lean mass (BFLM) as covariate, was used to compare mean BMD values. Adjusted for BFLM, there were no significant differences ( p > 0.05) in BMD at any site between sexes. There were no significant differences at the AP or LAT spine, FN, or WB between visit 1 and 5 for either sex. There was a significant increase in BMD ( p = 0.044) at the UD forearm over 2 years in males. However, 56% of the men ( n = 9) had a Z-score < -1.0 at the UD forearm. Seven of 11 women had Z-scores < -1.0 at the LAT spine and 4 of 13 had Z-scores < -1.0 at the AP spine. There were no significant changes in BMD at any site over the 2-year time frame, except a significant increase in BMD at the nondominant forearm in men. The spine appears to be an area of concern for women in this study when examining Z-score results. Coaches and medical staff need to continually educate collegiate endurance athletes about the importance of achieving and maintaining BMD through their college years.

Quantitative lateral flow immunoassay for rapid detection of procollagen type I N-terminal propeptide in the monitoring of osteoporosis treatment

Appropriate follow-up after treatment initiation in patients with osteoporosis is challenging. Serum biomarkers may offer more efficient monitoring of bone mineral density (BMD) than the currently used dual X-ray absorptiometry; however, significant changes in BMD often occur over at least 12 months. During teriparatide treatment for osteoporosis, monitoring with markers such as procollagen type I propeptide (PINP), which is derived from osteoblasts, can provide clinically useful information for disease management. However, rapid and cost-effective methods for detecting serum PINP are lacking, necessitating a point-of-care test (POCT) for enhanced follow-up efficiency in osteoporosis management. For the quantitative detection of PINP, we developed a high-sensitivity lateral flow immunoassay with a stacking pad (sLFIA). We established a calibration equation based on the test line/control line ratio obtained from our PINP sLFIA results of various nonspiked serum samples to calculate the PINP concentrations in 40 serum samples and compared the result with those obtained using a fully automated electrochemiluminescence immunoassay. PINP concentrations between these two methods exhibited excellent correlation (R = 0.991). In addition, we assessed the serum PINP concentrations of patients with osteoporosis treated with teriparatide. At the 3-month follow-up, their PINP levels were nearly twice as high as those at baseline, thus implying that our method can be used for osteoporosis treatment monitoring. Our findings thus indicate that the PINP sLFIA can serve as a POCT for monitoring medication response and managing osteoporosis.

Withdrawal of Denosumab in Patients With Primary Hyperparathyroidism: A Follow-up Report of the DENOCINA Study

ObjectivesWe investigated the development in the primary outcomes: changes in bone mineral density (BMD) measured by dual x-ray absorptiometry at the lumbar spine, total hip, and femoral neck after 2 years. MethodsIn patients with primary hyperparathyroidism, we investigated the effects of 30-mg cinacalcet per day plus 60 denosumab every 6 months for 1 year (Deno group), versus denosumab plus placebo for 1 year (DenoPlacebo-group), versus placebo plus placebo injection for 1 year (Placebo group). After the study’s termination, most patients receiving denosumab were switched to bisphosphonate treatment. ResultsForty-three out of 45 participants were subject to follow-up. A total of 35 patients completed a 2-year follow-up dual x-ray absorptiometry-scan (Deno: n = 13; DenoPlacebo: n = 12; and Placebo: n = 10). None of the groups showed statistically significant changes in BMD or experienced decreases in mean BMD below the study’s baseline level. Overall, the changes in T-scores from the final study measurement to follow-up were similar among the groups (P = .38 for lumbar spine T-score, .63 for total hip, and .97 for femoral neck by 1-way ANOVA). P-calcium was not different over time (P = .20 for change over time and P = .08 for the difference between the groups by repeated measures ANOVA). A total of 5 participants suffered a fracture during the study or follow-up periods, all but one was in the placebo group. ConclusionEvidence suggests that it is possible to at least maintain BMD, and thus potentially lower the fracture risk by a short course of denosumab followed by antiresorptive therapy, where applicable in patients with primary hyperparathyroidism.

Sarcopenia: an unsolved problem after hip fracture.

Sarcopenia, loss of muscle mass and strength, leads to functional dependence and disability. To date, no study reported the postoperative change of sarcopenia prevalence after hip fractures. Thus, we assessed postoperative changes in the prevalence of osteoporosis and sarcopenia in hip fracture patients. Among 1159 patients, who underwent surgery for low-energy hip fractures between May 2012 and December 2019, 224 patients (38 men and 186 women with a mean age of 76.8 ± 8.7years) were studied with preoperative and follow-up dual-energy X-ray absorptiometry (DXA). Bone mineral density (BMD) and skeletal muscle mass were measured on DXA scans. The postoperative changes in the prevalence of osteoporosis and that of the sarcopenia were evaluated as well as Koval grade of the hip fracture patients. While there was no significant change in BMD, SMI significantly decreased postoperatively. Mean decrease of the SMI was 0.53kg/m2 in men and 0.38kg/m2 in women. Prevalence of sarcopenia increased from 63 to 89% (p = 0.014) in men and from 45 to 57% (p = 0.006) in women. Lower BMI (Odds ratio (OR) 0.85 (95% confidence interval (CI) 0.76-0.96), p = 0.008) and prior sarcopenia (OR 14.47 (95% CI 5.29-35.39), p < 0.001) were the risk factors for the decrease of SMI after hip fracture. After hip fracture, osteoporosis seemed to be well managed and the prevalence of osteoporosis did not increase. However, SMI decreased and the prevalence of sarcopenia increased. More active measures are warranted to prevent sarcopenia in elderly hip fracture patients.

Even without changing the bone mineral density, alcohol consumption decreases the percentage of collagen, the thickness of bone trabeculae, and increases bone fragility.

Excessive alcohol consumption is considered a risk factor for bone health, as it causes a reduction in mass and increases the risk of fracture. However, the determination of bone mineral density (BMD) has not always been an adequate predictor of bone fragility. Thus, the hypothesis arises that chronic alcohol consumption interferes with collagen synthesis and the quality of bone trabeculae, with consequent bone fragility. Groups: Control (n = 6; water intake only during the entire study period); Ethanol (n = 6; ingestion of ethyl alcohol according to the protocol for inducing chronic alcohol consumption). The chronic alcohol consumption model did not cause a significant change in BMD, but there was a significant reduction of 20% in the thickness of the bone trabeculae and of 1.56% in the collagen located in the neck region of immature rat femurs. Although there was no significant change in the mineral matrix, the changes in the organic matrix were able to provide a significant reduction in bone strength. The results suggest harmful effects of alcohol intake on the bone quality of young adult animals and draw attention to the need to also consider methods for the diagnosis of collagen as an element of bone fragility.

The influence of lactation and its duration on bone mineral density in pregnancy and postpartum: A systematic review with meta-analysis.

There is a plethora of research on the association of parity and duration of lactation with bone mineral density (BMD) during and after pregnancy. However, there are no consensus conclusions on the impact of the duration of lactation on BMD. The aim of this study was to examine the effect of pregnancy, and the duration of lactation on BMD during pregnancy, postpartum phase and 12 months post-delivery. The search terms 'parity' 'lactation' 'BMD' were searched for using PubMed, CINAHL, SCOPUS and EMBASE databases in English language. Two independent reviewers assessed the quality of the included studies using Critical Appraisal Skills Program (CASP) appraisal tool and extracted data on BMD (g/cm2) in Excel. A meta-analysis was conducted with a random effect model using Cochrane Review Manager (Rev 5.4) to analyse the outcome. Heterogeneity was assessed with Chi Squared and I2 test. The duration of lactation was grouped into short lactation duration (SLD), ≤4 months and longer lactation duration (LLD)>6 months. Twenty-one studies were included in this review with four studies included in the meta-analysis. BMD reduced during pregnancy and lactation. Recovery and net gains in BMD followed weaning. However, at 12 months postpartum, women in the LLD group had significant losses at the lumbar spine while those in the SLD recovered BMD. Between the SLD and LLD groups, the change in BMD was not significant 0.48g/cm2 (95% CI -0.14, 1.10, p=0.13). BMD losses were greater in primiparous women than multiparous women. Women who breastfed for >6 months had significantly reduced BMD. However, compared to women that breastfed for a ≤4 months there was no significant change in BMD. Further investigation is needed to clarify the association between lactation and BMD in a postpartum population in those women extending breastfeeding beyond one year.

Short Communication: No Significant Changes in Weight and Body Fat Mass in Suppressed HIV-Infected Patients Switched to Dual Combination Lamivudine Plus Dolutegravir or Raltegravir.

Weight gain associated with integrase inhibitor-based treatment has become a critical issue in the clinical management of HIV infection. We analyzed changes in weight and body fat mass in 54 virologically suppressed patients who switched to lamivudine plus raltegravir or dolutegravir. Overall, after 12 months we reported a not significant increase in weight (median, +1.74 kg; p = .223) and total fat mass (median, +1.13 kg; p = .188), and these changes were comparable between groups. The median change in lumbar spine bone mineral density (BMD) [interquartile range (IQR)] was +0.02 g/cm2 (-0.02, +0.05; p = .786), and the median change in femur neck BMD (IQR) was +0.04 g/cm2 (-0.03, +0.06; p = .598), and changes were comparable between groups. In conclusion, the switch to dolutegravir/lamivudine or raltegravir/lamivudine dual therapy in virologically suppressed patients did not produce significant increases in weight and body fat mass after a 12-month follow-up, in association with not significant changes in BMD.

Effects of zonisamide monotherapy on bone health in drug-naive epileptic patients.

Alteration of bone strength is an adverse effect of antiepileptic drug treatment. We investigated the effects of zonisamide (ZNS) monotherapy on bone mineral density (BMD) and biomarkers of bone metabolism after 13months of treatment in drug-naive epileptic patients. Fifty-nine patients with new onset drug-naive epilepsy were enrolled (29 women, 30 men; mean age = 31.5±11.5years). The BMD and T scores were measured at the lumbar spine and femoral neck by using dual-energy X-ray absorptiometry. Biomarkers specific for bone metabolism (bone-specific alkaline phosphatase, parathyroid hormone, osteocalcin, insulinlike growth factor-1, C-telopeptide, and vitamin D3 levels) were measured before and after long-term ZNS monotherapy. Analysis of covariance (ANCOVA) was used to estimate BMD and biomarkers of bone metabolism before and after ZNS therapy. Age, sex, treatment duration, and ZNS dosage were included as covariates for adjustment in the ANCOVA model. Furthermore, subgroup analyses were performed for each sex, and the effect size was calculated. After 13months of ZNS treatment, the BMD and T scores at the lumbar spine (L1-L4 level) and femoral neck were not significantly different. Moreover, the biochemical markers showed no significant differences after ZNS monotherapy. Women showed significantly decreased baseline BMD at the femoral neck compared to men (P=.026), although the mean age and body mass index were not significantly different between the sexes. No significant changes in BMD or biomarkers of bone metabolism were seen in either sex after 13months of ZNS treatment. The results suggest that long-term ZNS monotherapy does not affect bone health in drug-naive patients with epilepsy negatively.

Effects of Hepatitis C Virus (HCV) Eradication on Bone Mineral Density in Human Immunodeficiency Virus/HCV-Coinfected Patients.

Little is known about the effects of eradication of hepatitis C virus (HCV) on bone mineral density (BMD) and biomarkers of bone remodeling in human immunodeficiency virus (HIV)/HCV-coinfected patients. We prospectively assessed standardized BMD (sBMD) at the lumbar spine and femoral neck, World Health Organization BMD categories at both sites, and plasma concentrations of soluble receptor activator of NF-κβ ligand (sRANKL), and osteoprotegerin (OPG) at baseline (the date of initiation of anti-HCV therapy) and at 96 weeks. A total of 238 patients were included. The median age was 49.5 years, 76.5% were males, 48.3% had cirrhosis, 98.3% were on antiretroviral therapy, median CD4+ cell count was 527 cells/μL, and 86.6% had HIV-1 RNA <50 copies/mL. The prevalence of osteoporosis at baseline at the lumbar spine (LS) and femoral neck (FN) was 17.6% and 7.2%, respectively. Anti-HCV therapy comprised pegylated interferon (peg-IFN) and ribavirin (RBV) plus 1 direct-acting antiviral in 53.4%, peg-IFN/RBV in 34.5%, and sofosbuvir/RBV in 12.2%. A total of 145 (60.9%) patients achieved sustained virologic response (SVR). No significant effect of SVR was observed on sBMD for the interaction between time and SVR either in the LS (P = .801) or the FN (P = .911). Likewise, no significant effect of SVR was observed in plasma levels of sRANKL (P = .205), OPG (P = .249), or sRANKL/OPG ratio (P = .123) for the interaction between time and SVR. No significant correlation was found between fibrosis by transient elastography, and LS and FN sBMD, at baseline and week 96. SVR was not associated with significant changes in BMD nor biomarkers of bone remodeling in HIV/HCV-coinfected persons.

Trabecular bone deterioration in differentiated thyroid cancer: Impact of long-term TSH suppressive therapy.

BackgroundConflicting results has been reported regard osteoporosis and fractures in patients with Differentiated Thyroid Cancer (DTC). Our objective was to evaluate the long‐term effects of TSH suppression therapy with Levothyroxine (LT4) on trabecular bone score (TBS) and bone mineral density (BMD) in females with DTC after thyroidectomy.MethodsAbout 145 women with resected DTC and receiving long‐term TSH therapy, were stratified according to the degree of TSH suppression. Mean duration of follow‐up was 12.3 ± 6.1 years. BMD and TBS, were assessed using dual‐energy X‐ray absorptiometry (DXA) and TBS iNsight (Med‐Imaps), at baseline (1‐3 months after surgery) and at the final study visit.ResultsIn patients stratified by duration of TSH suppression therapy (Group I, 5‐10 years; Group II, >10 years), slight increases from baseline TSH levels were observed. Significant decreases in LS‐BMD and FN‐BMD were seen in patients after >10 years. TBS values were lower in Groups I (1.289 ± 0.122) and II (1.259 ± 0.129) compared with baseline values (P = .0001, both groups). Regarding the degree of TSH suppression, TBS was significantly reduced in those with TSH < 0.1 µU/mL (P = .0086), and not in patients with TSH suppression of 0.1.‐0.5 or >0.5 µU/mL.ConclusionsWe found deterioration of trabecular structure in patients with DTC and TSH suppression therapy below 0.1 µU/mL and after 5‐10 years of follow‐up. Significant changes in BMD according to TSH levels were not observed. Trabecular Bone Score is a useful technique for identifying thyroid cancer patients with risk of bone deterioration.

SUN-377 Efficacy of Low Dose Denosumab in Maintaining Bone Mineral Density in Postmenopausal Women with Osteoporosis: A Real World, Prospective Observational Study

Introduction: Denosumab, a fully human monoclonal antibody to RANK-ligand, has been shown to increase bone mineral density (BMD) and reduce the risk of hip, vertebral and non-vertebral fractures in postmenopausal women with osteoporosis (1-3). Varying doses of denosumab including 30mg/3months have demonstrated a decrease in bone remodelling in a dose-dependent manner (2,4-6). The primary objective of this study is to evaluate the efficacy of low dose denosumab (30mg/6 months) in postmenopausal women with osteoporosis who are reluctant to consider or continue the full dose of denosumab due to adverse events (AE) or concerns of potential AE. Methods: Following informed consent, postmenopausal women with a T-score of ≤ -2.5 at the lumbar spine (LS) or at the total hip (TH) received denosumab 30mg/6months. Patients with an additional skeletal disorder, prior fragility fracture, or on oral steroids (daily in the past 12 months) were excluded. The primary endpoint was the percent change in BMD at the lumbar spine (LS), total hip (HP), femoral neck (FN) and 1/3 radius (1/3R) at 12 months. Secondary outcomes were 1) percent change in BMD at the LS, TH, FN, and 1/3R at 24 months and 2) AE. Results: We enrolled 183 patients. The mean age was 69 years (SD= 7.07), 80% of patients had a moderate fracture risk (CAROC tool), 3% were current smokers and 9% consumed alcohol daily. 14.4% of patients were on SSRI/SNRI, 9.6% were on PPI, and no patient was on an aromatase inhibitor. At 12 months (n=125), the mean BMD significantly increased by +2.0% (95% CI 2.8%-1.3%) at the LS (p<0.001). There was no significant change in BMD at the FN, TH, AND 1/3R. At 24 months (n=65), the percent change in BMD was +3.4% (95% CI 4.8%-2.0%: p<0.001) at the LS, +1.5% (95% CI 2.9%-0.15%: p=0.031) at the FN, +1.9% (95% CI 3.5%-0.24%: p=0.025) at the 1/3R. There was no significant change in BMD at the TH. Conclusion: Low dose denosumab appears to be effective in maintaining BMD in postmenopausal women with a moderate fracture risk and may be of benefit in individuals who are experiencing side effects or concerns of side effects. This may also be of value following 10 years of therapy in order to maintain BMD.

The influence of a sustained 10-day hypoxic bed rest on cartilage biomarkers and subchondral bone in females: The FemHab study.

This study assessed the influence of a 10‐day hypoxic bed rest on cartilage biomarkers and subchondral bone density across the patellofemoral joint (PFJ). Within clinical settings hypoxic tissue may arise in several types of disorders. Furthermore, a hypoxic environment is being considered for space flight habitats in the near future. Female participants (N = 12) participated in this study comprising three 10‐day interventions: hypoxic ambulation (HAMB), normoxic bed rest (NBR), and hypoxic bed rest (HBR). Venous samples were collected prior to (day −2: Pre) and during the intervention (days 2 and 5), immediately before reambulation (D11) and 24 hr post intervention (R1). Blood samples were analyzed for: aggrecan, hyaluronan, Type IIA procollagen amino terminal propeptide (PIIANP), and cartilage oligomeric matrix protein (COMP). Total bone mineral density (BMD) in eight regions (2 mm × 10 mm) across the PFJ was determined. The three interventions (HAMB, HBR, and NBR) did not induce any significant changes in the cartilage biomarkers of hyaluronan or PIIANP. Aggrecan increased during the HAMB trial to 2.02 fold the Pre value. COMP decreased significantly in both NBR & HBR compared to HAMB on D5. There were significant differences in BMD measured across the PFJ from cortical patellar bone (735 to 800 mg/cm3) to femur trabecular (195 to 226 mg/cm3). However, there were no significant changes in BMD from Pre to Post bed rest. These results indicate that there were no significant detectable effects of inactivity/unloading on subchondral bone density. The biomarker of cartilage, COMP, decreased on D5, whereas the addition of hypoxia to bed rest had no effect, it appears that hypoxia in combination with ambulation counteracted this decrease.

A 12-month continuous and intermittent high-impact exercise intervention and its effects on bone mineral density in early postmenopausal women: a feasibility randomized controlled trial.

Intermittent mechanical loading generates greater bone adaptations than continuous mechanical loading in rodents but has never been evaluated in humans. This study aimed to evaluate the feasibility of a continuous and intermittent countermovement jump (CMJ) intervention for attenuating early postmenopausal BMD loss. 41 healthy early postmenopausal women (age=54.6±3.4 years) were randomly assigned to a continuous countermovement jumping group, an intermittent countermovement jumping group or a control group for 12 months. Adherence and dropout rates were recorded along with bone mineral density (BMD) at lumbar spine, femoral neck and trochanter sites at baseline, 6 months and 12 months. 28 participants completed the study. Dropout rate during the intervention (from the initiation of exercise) was 36% from continuous and 38% from intermittent countermovement jumping groups. For the participants that completed the intervention, adherence was 60.0±46.8% for continuous and 68.5±32.3% for intermittent countermovement jumping. The control group lost significant lumbar spine BMD (% difference=-2.7 [95%CI: -3.9 to -1.4]) and femoral neck BMD (% difference=-3.0% [95%CI: -5.1 to -0.8]). There was no statistically significant change in BMD for either countermovement jumping group. There was no statistically significant difference in BMD change between continuous or intermittent countermovement jumping groups when compared with the control group. Adherence and dropout rates were in line with previous similar interventions. To evaluate the effect of continuous and intermittent exercise on BMD, future studies should focus on maintaining participant engagement and adherence to the exercise intervention.

Bone remodeling of the proximal tibia after uncemented total knee arthroplasty: secondary endpoints analyzed from a randomized trial comparing monoblock and modular tibia trays—2 year follow-up of 53 cases

Background and purpose — Bone remodeling as a response to bone trauma, postoperative immobilization, and device-related bone reactions can lead to loss of bone stock and increase the risk of periprosthetic fracture and aseptic loosening. This study investigates the adaptive bone remodeling of the proximal tibia after uncemented total knee arthroplasty (TKA).Patients and methods — We performed a 2-year follow up of 53 patients (mean age 62 (38–70) years, 27 of whom were men, who received an uncemented TKA in a randomized controlled trial with bone mineral density (BMD) as secondary endpoint. Patients were randomized to 2 groups of either monoblock (A) or modular (B) polyethylene design. The TKAs were performed using the uncemented Zimmer Nexgen trabecular metal. Measurements of BMD were done postoperatively and after 3, 6, 12, and 24 months. BMD was measured in 3 regions of interest (ROI).Results and interpretation — In group A statistically significant changes in BMD were seen after 24 months in both the medial and lateral ROI. BMD decreased medially by 15% (p = 0.004) and laterally by 13% (p = 0.01). In group B the BMD changes were limited and after 24 months returned to the preoperative values. The differences in BMD change between groups were statistically significant in both the medial (p = 0.03) and lateral (p = 0.02) ROI. In the distal ROI we found no significant change in BMD in either group. A significantly different bone remodeling pattern of the proximal tibia was seen in the 2 groups with a higher degree of bone loss in the knees that received the monoblock polyethylene design, indicating that the flexible monoblock implant design, previously shown to improve fixation, does not decrease the bone loss of the proximal tibia.Trial registration: ClinicalTrials.gov identifier: NCT01637051.

The renin-angiotensin aldosterone system and osteoporosis: findings from the Women's Health Initiative.

Pharmacological inhibitors of the renin-angiotensin aldosterone system (RAAS) are used to treat hypertension. However, the relationship of these medications to osteoporosis is inconsistent, and no study has included simultaneous measurements of both incident fractures and bone mineral density (BMD). The association of RAAS inhibitor use (n = 131,793) with incident fractures in new users of these medications in women in the Women's Health Initiative over a minimum median follow-up of 6.5years was assessed by Cox proportional hazard models. The association of incident fractures by a cumulative duration of use of these medications (<3years.) and (> 3years.) was also estimated. Subgroup analysis of fracture risk by RAAS inhibitor use confined to women with hypertension was also performed (n = 33,820). The association of RAAS inhibitor use with changes in BMD of the hip was estimated by linear regression in 8940 women with dual energy X-ray absorptiometry measurements. There was no significant association between RAAS inhibitor use and all fractures in the final adjusted multivariable models including hip BMD (HR 0.86 (0.59, 1.24)). However, among users of RAAS inhibitors, including ACE inhibitors and angiotensin receptor blockers (ARBs), hazard ratios for all incident fracture sites in final multivariable models including hip BMD showed dramatic differences by duration of use, with short duration of use (3years or less) associated with a marked increased risk for fracture (HR 3.28 (1.66, 6.48)) to (HR 6.23 (3.11, 12.46)) and use for more than 3years associated with a reduced fracture risk (HR 0.40 (0.24, 0.68) to (HR 0.44 (0.20, 0.97)) . Findings were similar in the subgroup of women with a history of hypertension. There was no significant change in BMD of the hip by RAAS inhibitor use. In postmenopausal women, use of RAAS inhibitors, including ACE inhibitors and ARBs, is associated with an increased risk for fracture among new users of these medications in the first 3years of use. However, long-term use (> 3years) is associated with a reduced risk. Consideration for fracture risk may be part of the decision-making process for initiation of these medications for other disease states.

SAT-LB052 Intravenous Bisphosphonate Therapy in Children with Spinal Muscular Atrophy

Introduction: Children with Spinal Muscular Atrophy (SMA) are at high risk for poor bone health with 50% of the most severely affected patients reporting at least one fragility fracture prior to age 10 years. Intravenous bisphosphonate (IV BP) has been used for treatment of disuse osteoporosis, primarily in children with cerebral palsy or muscular dystrophy. Our group has previously demonstrated that children with secondary osteoporosis are at increased risk for developing acute adverse events following IV BP but the safety and efficacy of IV BP in SMA population have not been studied. Objective: To evaluate safety profile and the efficacy of IV BP for treatment of concerns for osteoporosis in children with SMA. Methods: We retrospectively reviewed IV BP use in children with SMA at a tertiary pediatric center from 2010 to 2018. Demographic data, fractures history, laboratory indices, and bone mineral density (BMD) by DXA were obtained from electronic medical record and are presented in this case series. Results: Eight children (50% female; 75% SMA type I, 25% SMA type II) were included in this study. The median age of first IV BP infusion was 6.7 years (range 2.3 - 19.0 years). Six had long bone fractures (total of 15) prior to IV BP treatment; two of these fractures were healing fractures discovered 1 month after IV BP started. Two patients were treated based on declining BMD. Patients received a total of 39 infusions (54% pamidronate, 46% zoledronic acid). All received their first IV BP in an inpatient setting due to need for monitoring of respiratory support (BiPAP). Acute phase reactions occurred following 38% (3/8) and 3% (1/31) of initial and subsequent infusions, respectively. All were considered mild and no adverse respiratory events were noted. Hypocalcemia was observed following 5% of infusions (2/37). Hypophosphatemia was common (73%, 27/37) but rarely required intravenous replacement. There was no significant change in BMD at 1 year pre- and post-IV BP treatment among four who had DXA scans for comparison. In 32.7 patient years of follow up, two patients (25%) had total of 3 subsequent fractures, including an occurrence of atypical femur fracture which was observed in one patient 3 years after initiation of IV BP. Conclusion: Although the acute adverse events from IV BP therapy were generally mild, caution needs to be taken given the occurrence of an atypical femur fracture in this population. More follow up is needed to determine the efficacy of therapy in maintaining BMD and preventing further fracture in patients with disuse osteoporosis secondary to SMA. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Effects of resveratrol on bone health in type 2 diabetic patients. A double-blind randomized-controlled trial

ObjectivesPatients with type 2 diabetes (T2DM) are at increased fracture risk. Resveratrol has shown beneficial effects on bone health in few studies. The aim of this trial was to investigate the effects of resveratrol on bone mineral density (BMD) and on calcium metabolism biomarkers in T2DM patients.MethodsIn this double-blind randomized placebo-controlled trial 192 T2DM outpatients were randomized to receive resveratrol 500 mg/day (Resv500 arm), resveratrol 40 mg/day (Resv40 arm) or placebo for 6 months. BMD, bone mineral content (BMC), serum calcium, phosphorus, alkaline phosphatase, and 25-hydroxy vitamin D were measured at baseline and after 6 months.ResultsAt follow-up, calcium concentrations increased in all patients, while within-group variations in alkaline phosphatase were higher in both resveratrol arms, and 25-hydroxy vitamin D increased in the Resv500 arm only, without between-group differences. Whole-body BMD significantly decreased in the placebo group, while whole-body BMC decreased in both the placebo and Resv40 arms. No significant changes in BMD and BMC values occurred in the Resv500 arm. The adjusted mean differences of change from baseline were significantly different in the Resv500 arm vs placebo for whole-body BMD (0.01 vs −0.03 g/cm2, p = 0.001), whole-body BMC (4.04 vs −58.8 g, p < 0.001), whole-body T-score (0.15 vs −0.26), and serum phosphorus (0.07 vs −0.01 µmol/L, p = 0.002). In subgroup analyses, in Resv500 treated-patients BMD values increased to higher levels in those with lower calcium and 25-hydroxy vitamin D values, and in alcohol drinkers.ConclusionsSupplementation with 500 mg resveratrol prevented bone density loss in patients with T2DM, in particular, in those with unfavorable conditions at baseline.