Increase In Bone Mineral Density Research Articles

THU434 A Case Of An Atypical Femur Fracture Managed Medically With Teriparatide

Abstract Disclosure: S.V. Rupani: None. A. Kotwal: None. L. Graeff-Armas: None. Atypical femur fractures (AFFs) are atraumatic or low-trauma femur fractures located in the sub-trochanteric region or femoral shaft. AFFs represent around 0.5% of all femur fractures. The increased use of bisphosphonates has led to a rise in the incidence of AFFs as it has emerged as a potential complication. While the mechanism of bisphosphonate-related AFFs has yet to be elucidated, one proposed mechanism is that bisphosphonates can cause over-suppression of bone turnover. If over-suppression is a contributing factor, then hypothetically, anabolic therapy can help heal existing fractures and prevent impending fractures by reversing over-suppression. Numerous animal models have demonstrated that parathyroid hormone and teriparatide enhance fracture healing. However, clinical trials and meta-analyses on the effects of teriparatide in fracture healing have been equivocal. There have been both retrospective and prospective studies, along with anecdotal reports demonstrating the benefits of teriparatide in healing in AFFs. However, there have been no randomized controlled trials assessing the efficacy of teriparatide in AFFs. Based on this limited evidence, the American Society for Bone and Mineral Research recommends considering teriparatide in patients who have failed conservative therapy. We present a case of an incomplete AFF in the setting of short-term bisphosphonate use that was managed with teriparatide in addition to conservative measures. Our patient presented with a complete right AFF treated surgically and an incomplete left AFF that we managed medically with teriparatide. Repeat left femur imaging six months after starting teriparatide therapy showed interval callus formation consistent with a healed fracture. Right femur imaging also showed a healing proximal femoral shaft fracture status post intramedullary fixation. She completed twenty-five months of teriparatide therapy and did not sustain any interval fractures. Repeat imaging one year after completion of teriparatide therapy continued to show a stable healed left AFF, along with a healed right AFF. She is currently more than two years post-completion of teriparatide and has remained fracture free. This case highlights the role that teriparatide may have as an option for medical management in incomplete AFFs and to accelerate healing in complete AFFs that have been managed surgically. Furthermore, with therapeutic options for osteoporosis management limited in the post-AFF setting, teriparatide helps increase bone mineral density and reduce future fracture risk. Randomized controlled trials are needed to draw definite conclusions on the efficacy of teriparatide in managing AFFs. However, this is difficult given the rare occurrence of AFFs. Therefore, case reports like ours offer insight into when teriparatide may be helpful in managing AFFs. Presentation: Thursday, June 15, 2023

FRI675 Higher FSH Level Is Associated With Increased Risk Of Incident Hip Fracture In Older Adults, Independent Of Sex Hormone Levels

Abstract Disclosure: E.H. Koh: None. S.K. Ewing: None. S. Sigurdsson: None. V. Guðnason: None. T.F. Hue: None. E. Vittinghoff: None. M. Zaidi: Research Investigator; Self; patents on FSH, bone, body fat and neurodegeneration. Held by Icahn School of Medicine and Mount Sinai. C.J. Rosen: None. C. Ohlsson: None. L. Grahnemo: None. Å. Tivesten: None. A.V. Schwartz: None. A.L. Schafer: None. Higher levels of follicle stimulating hormone (FSH) are associated with bone loss among women during the perimenopausal transition and among older men, independent of sex hormone levels. In vitro studies have shown bone remodeling via FSH-receptors on bone cells. Furthermore, treating ovariectomized mice with FSH-blocking polyclonal antibodies results in increased bone mineral density. However, it is uncertain whether this association of FSH elevation and bone loss translates to increased fracture risk. To examine the relationship between FSH and incident hip fracture, independent of sex hormone levels, we used a case-cohort design to sample from the AGES-Reykjavik cohort, a longitudinal cohort of 5764 older Icelandic adults designed to assess gene/environment interactions and their relationship to diseases in old age. Baseline visits took place from 2002 and through 2006. We excluded those with prior hip fracture, those whose quantitative computed tomography bone mineral density scan quality was unacceptable, or who were taking sex hormone replacement, sex hormone antagonists, or glucocorticoid medications. We randomly sampled, stratified by sex, 147 women and 148 men to form our subcohort. Our cases were comprised of a random sample, stratified by sex, of 133 women and 122 men (of whom 25 were in the subcohort) who sustained incident hip fracture within 10 years of the baseline visit. Fractures were adjudicated and recorded in the AGES-Reykjavik fracture registry. FSH and sex hormone binding globulin (SHBG) were measured on baseline serum by immunoassay and estradiol and total testosterone by mass spectrometry. Robust weighted Cox proportional hazards models were used to determine the relationship between FSH and subsequent risk of hip fracture, with adjustment for covariates. Among the subcohort, mean age was 76 years. In women, mean ± SD FSH was 64.4 ± 25.5 IU/L with estradiol 5.7 ± 4.2 pg/mL, testosterone 22.5 ± 10.4 ng/dL, and SHBG 74.0 ± 33.8 nmol/L. In men, mean FSH was 12.2 ± 11.9 IU/L with estradiol 21.3 ± 6.9 pg/mL, testosterone 457.9 ± 171.2 ng/dL, and SHBG 52.8 ± 17.5 nmol/L. No interaction was identified between FSH and sex for the relationship with fracture, so men and women were pooled for analysis. Higher levels of FSH were associated with a significant increased risk of incident hip fracture in models adjusted for age and sex [hazard ratio (HR) 1.24 (95% CI 1.04-1.48, p=0.02)] and after further adjustment for estradiol, testosterone, and SHBG levels [HR 1.20 (95% 1.01-1.44, p=0.04)] per sex-specific SD increase in FSH level. Our findings support a growing body of evidence for direct pleiotropic effects of FSH on bone. FSH may contribute to aging and disability independent of sex hormone levels. Presentation: Friday, June 16, 2023

SAT183 What Determines Bone Mineral Density Changes After Successful Parathyroidectomy In Primary Hyperparathyroidism?

Abstract Disclosure: J.E. Mosquera: None. X. Li: None. N. Maalouf: None. Background: Parathyroidectomy (PTX) is the only cure for primary hyperparathyroidism (PHPT). However, the impact of PTX on bone mineral density (BMD) is very variable. Methods: To assess the impact of demographic and clinical characteristics on BMD change post-PTX, we retrospectively reviewed charts of patients with biochemically proven PHPT and successful PTX between 2006 and 2022 at our institution and who had available pre- and post-PTX DXA scans. We extracted available demographic, clinical, and laboratory data including age, gender, race, body mass index, pre-PTX serum parathyroid hormone, calcium, phosphorus, alkaline phosphatase (Alkphos), 25-OH-vitamin D, and creatinine, 24-hour urine calcium, and use of bisphosphonates. The association between these parameters and BMD changes were assessed using univariate and multivariate models. Results: 121 patients (107 women) were included in this analysis. 35% were African American and 50% Hispanic. At PTX, mean (SD) age was 59 (12) years, BMI was 33 (7) kg/m2. 36% had osteopenia and 47% had osteoporosis on pre-PTX DXA. 6% of patients used BP before PTX and 3% used BP within one year of PTX. At year 1 post-PTX, median BMD (25th-75th percentile) change was +2.7% (-0.2% - +6.6%) at the lumbar spine (LS), +2.4% (-0.5% - +5.9%) at the femoral neck (FN), +2.8% (0.7% - +4.7%) at total hip (TH), and +0.1% (-3.6% - +3.0%) at the 1/3 radius. In univariate analyses, 1-year change in FN BMD was positively associated with highest pre-PTX serum calcium, PTH, and Alkphos, and negatively associated with age and serum creatinine. TH BMD change at 1 year was positively associated with highest pre-PTX PTH and Alkphos, and negatively associated with lowest T-score at baseline, age, and pre-PTX serum phosphorus, 25-OH-D and creatinine. LS BMD change at 1 year was positively associated with highest pre-PTX serum calcium and PTH, and negatively associated with lowest phosphorus pre-PTX. In multivariate analyses, younger age, highest pre-PTX serum calcium, and lowest BMD T-score pre-PTX were all independently and significantly associated with greater increase in post-PTX BMD at the FN, TH, and LS. Moreover, pre-PTX Alkphos was associated with greater BMD gain at the FN and TH, while female gender was associated with greater gain in LS BMD. Conclusions: In patients with PHPT who undergo curative PTX, variable BMD changes are observed at 1-year post-PTX. Younger age at PTX, higher serum calcium, and lower BMD pre-PTX are all associated with greater BMD gains post-PTX. These findings should be considered in the counseling of PHPT patients undergoing PTX. Presentation: Saturday, June 17, 2023

FRI038 Differences In Bone Accrual Over One Year In Young Girls With Obesity Compared To Normal Weight Controls

Abstract Disclosure: S. Kaur: None. V. Singhal: None. L.A. Haidar: None. M. Bredella: None. M. Misra: None. Introduction: Despite higher bone mineral density (BMD), women with obesity are at an increased risk of fracture compared to normal-weight women. Optimal adolescent bone accrual is critical for normal peak bone mass acquisition and future bone health. Whereas several studies have examined the impact of low body weight on bone accrual in youth, data are lacking regarding the impact of obesity on bone accrual. We aimed to assess changes in areal and volumetric BMD, bone geometry and microarchitecture, and estimates of bone strength over one year in young females with moderate to severe obesity compared to their normal-weight counterparts. Methods: We recruited females between 13-25 years of age with moderate to severe obesity (OB) (n=21) and compared their bone accrual over one year with normal-weight controls (NWC) (n=50). Dual-energy X-ray absorptiometry to assess areal BMD (aBMD), high-resolution peripheral quantitative computed tomography (distal radius and tibia) to assess volumetric BMD (vBMD), bone geometry, and microarchitecture, and micro finite element analysis for estimates of bone strength was used. Analyses were controlled for age and race. Results: The mean age was 18.7 ± 2.7 years. OB and NWC were similar for age, race, height, and physical activity at baseline. OB had higher weight and BMI (p<0.0001 for both) and younger menarchal age (p=0.022) than NWC. Over one year, there was no difference between the groups for change in height, weight, and BMI. However, OB did not demonstrate the increase in total hip BMD observed in NWC (p=0.03) over a year. OB also had lesser increases in percent cortical area, cortical thickness, cortical and total vBMD at the radius over a year than the NWC group (p≤0.037 for all). The groups did not differ for tibial bone accrual. Conclusions: Our study demonstrates that longitudinal bone accrual over one year is impaired at the total hip and radius in adolescents and young adult females with obesity compared to normal-weight controls, while no differences are observed in tibial bone accrual. This raises concerns regarding future bone health in women with obesity, particularly at certain skeletal sites. Presentation: Friday, June 16, 2023

SAT182 Effects Of An Orally Bioavailable Nonpeptide Parathyroid Hormone Receptor Type 1 (PTH1R) Antagonist In Rodent Models Of Primary Hyperparathyroidism (PHPT)

Abstract Disclosure: A.S. Antwan: Employee; Self; Crinetics Pharmaceuticals. E. Rico-Bautista: Employee; Self; Crinetics Pharmaceuticals. J. Pontillo: Employee; Self; Crinetics Pharmaceuticals. S. Wang: Employee; Self; Crinetics Pharmaceuticals. M. Johns: Employee; Self; Crinetics Pharmaceuticals. B. Ramms: Employee; Self; Crinetics Pharmaceuticals. M.A. Fowler: Employee; Self; Crinetics Pharmaceuticals. J.B. Nguyen: Employee; Self; Crinetics. A.A. Castellanos Gonzalez: Employee; Self; Crinetics. B. Fleck: Employee; Self; Crinetics Pharmaceuticals. K. Retting: Employee; Self; Crinetics Pharmaceuticals. D. Dalvie: Employee; Self; Crinetics Pharmaceuticals. S.F. Betz: Employee; Self; Crinetics Pharmaceuticals. S. Markison: Employee; Self; Crinetics Pharmaceuticals. Primary hyperparathyroidism (PHPT) is a condition resulting from an over-secretion of parathyroid hormone (PTH) from one or more overactive parathyroid glands. PTH is a peptide hormone that regulates blood calcium concentrations through effects on bone, intestines, and kidney. PTH acts on parathyroid hormone receptor type 1 (PTH1R) in the kidney to increase calcium reabsorption and block phosphate reabsorption. The loss of phosphate ions then causes an increase in ionized calcium in the blood and cAMP in the urine. At the bone, continuous PTH infusion stimulates osteoclast activity while inhibiting osteoblast activity, leading to breakdown of bone and release of calcium into the extracellular fluid. Conditions that cause excess PTH, such as PHPT, result in elevated concentrations of plasma calcium, increased bone loss, increased fracture risk, and higher susceptibility to kidney stone development. PHPT affects approximately 100,000 patients per year, but many patients are asymptomatic and remain undiagnosed. While a partial or total parathyroidectomy may be suitable for patients diagnosed with severe cases of PHPT, there are limited treatment options for those who do not meet the criteria or do not wish to undergo surgery. The goals for medicinal treatment are to normalize blood calcium levels and urinary calcium excretion, as well as increase bone mineral density to reduce fracture risk. Blocking PTH action directly via a potent PTH1R antagonist may provide an important new therapeutic mechanism to treat patients with PHPT. Using iterative medicinal chemistry and pharmacology, Crinetics has identified several potent and orally bioavailable PTH1R antagonists with good drug-like properties. Lead molecules were evaluated in vivo in preclinical rodent models for their ability to suppress the effects of excess PTH on serum calcium, bone turnover, and cAMP levels in the kidney. One of these compounds, ANT-5, was characterized as a potent negative allosteric modulator of both human and rat PTH1R. In rats, oral administration of ANT-5 dose-dependently suppressed PTH-induced hypercalcemia. ANT-5 also suppressed PTH-stimulated urinary cAMP in rats, indicating its ability to inhibit the actions of PTH in the kidney. We further evaluated the effect of ANT-5 in a rodent model of continuous PTH infusion-induced bone turnover. Once-daily oral administration of ANT-5 mitigated PTH-induced bone resorption, suggesting that inhibiting PTH1R may have beneficial clinical effects on bone density. The culmination of these studies has led to a subset of candidate molecules that are being evaluated in safety studies to identify the compound(s) suitable for evaluation in human clinical trials. Support: Crinetics Pharmaceuticals. Presentation: Saturday, June 17, 2023

Molecular Complex of HSIM-loaded Polymeric Nanoparticles: Potential Carriers in Osteoporosis.

Statins, especially simvastatin promote bone formation by stimulating the activity of osteoblasts and suppressing osteoclast activity via the BMP-Smad signaling pathway. Statins present the liver first-pass metabolism. This study attempts to fabricate and evaluate simvastatin functionalized hydroxyapatite encapsulated in poly(lactic-co-glycolic) acid (PLGA) nanoparticles (HSIM-PLGA NPs) administered subcutaneously with sustained release properties for effective management of osteoporosis. Simvastatin functionalized hydroxyapatite (HSIM) was prepared by stirring and validated by docking studies, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and X-ray diffraction (XRD). Further, HSIM-loaded PLGA nanoparticles (HSIM-PLGA NPs) were developed via the solvent emulsification method. The nanoparticles were evaluated for zeta potential, particle size, entrapment efficiency, stability studies, and in vitro drug release studies. in vitro binding affinity of nanoparticles for hydroxyapatite was also measured. Bone morphology and its effect on bone mineral density were examined by using a glucocorticoid-induced osteoporosis rat model. The optimized nanoparticles were found to be amorphous and showed no drug-polymer interaction. The particle size of formulated nanoparticles varied from 196.8 ± 2.27nm to 524.8 ± 5.49 nm and the entrapment efficiency of nanoparticles varied from 41.9 ± 3.44% to 70.8 ± 4.46%, respectively. The nanoparticles showed sustained release behaviour (75% in 24 hr) of the drug followed by non-fickian drug release. The nanoparticles exhibited high binding affinity to bone cell receptors, increasing bone mineral density. A significant difference in calcium and phosphorous levels was observed in disease and treatment rats. Porous bone and significant improvement in porosity were observed in osteoporotic rats and treated rats, respectively (P < 0.05). Bone-targeting nanoparticles incorporating functionalized simvastatin can target bone. Thus, in order to distribute simvastatin subcutaneously for the treatment of osteoporosis, the developed nanoparticles may act as a promising approach.

Cleft palate and minor metabolic disturbances in a mouse global Arl15 gene knockout.

ARL15, a small GTPase protein, was linked to metabolic traits in association studies. We aimed to test the Arl15 gene as a functional candidate for metabolic traits in the mouse. CRISPR/Cas9 germline knockout (KO) of Arl15 showed that homozygotes were postnatal lethal and exhibited a complete cleft palate (CP). Also, decreased cell migration was observed from Arl15 KO mouse embryonic fibroblasts (MEFs). Metabolic phenotyping of heterozygotes showed that females had reduced fat mass on a chow diet from 14 weeks of age. Mild body composition phenotypes were also observed in heterozygous mice on a high-fat diet (HFD)/low-fat diet (LFD). Females on a HFD showed reduced body weight, gonadal fat depot weight and brown adipose tissue (BAT) weight. In contrast, in the LFD group, females showed increased bone mineral density (BMD), while males showed a trend toward reduced BMD. Clinical biochemistry analysis of plasma on HFD showed transient lower adiponectin at 20 weeks of age in females. Urinary and plasma Mg2+ concentrations were not significantly different. Our phenotyping data showed that Arl15 is essential for craniofacial development. Adult metabolic phenotyping revealed potential roles in brown adipose tissue and bone development.

Anti-Osteoarthritic Effects of Antarctic Krill Oil in Primary Chondrocytes and a Surgical Rat Model of Knee Osteoarthritis.

Osteoarthritis (OA) is characterized by progressive cartilage destruction and synovitis; however, there are no approved disease-modifying OA drugs. Krill oil (KO) has been reported to possess anti-inflammatory properties and alleviate joint pain in knee OA, indicating its potential to target the inflammatory mechanism of OA. Therefore, the anti-OA effects of KO were investigated in primary chondrocytes and a surgical rat model of knee OA. The oral administration of KO at 200 and 100 mg/kg for 8 weeks improved joint swelling and mobility in the animal model and led to increased bone mineral density and compressive strength in the cartilage. The oral KO doses upregulated chondrogenic genes (type 2 collagen, aggrecan, and Sox9), with inhibition of inflammation markers (5-lipoxygenase and prostaglandin E2) and extracellular matrix (ECM)-degrading enzymes (MMP-2 and MMP-9) in the cartilage and synovium. Consistently, KO treatments increased the viability of chondrocytes exposed to interleukin 1α, accompanied by the upregulation of the chondrogenic genes and the inhibition of the ECM-degrading enzymes. Furthermore, KO demonstrated inhibitory effects on lipopolysaccharide-induced chondrocyte inflammation. Histopathological and immunohistochemical analyses revealed that KO improved joint destruction and synovial inflammation, probably due to the anti-inflammatory, anti-apoptotic, and chondrogenic effects. These findings suggest the therapeutic potential of KO for knee OA.

P03 Long term denosumab treatment in osteoporosis - a case series

Abstract Introduction Studies have shown that denosumab reduces fracture risk and increases bone mineral density and is associated with low adverse events over 10 years. We have reviewed 3 patients in our hospital who have been successfully treated with denosumab 20 injections. Case description Clinical details of these patients are outlined in the table. Discussion All three patients have responded well to denosumab therapy with definite improvement of T scores and positive bone mineral density change compared to baseline, in both spine and hip regions. They have not experienced significant side effects related to treatment. The second patient was treated as possible fracture as the x-rays were not convincing of definitive fracture. Patient 3, despite having very low T scores and multiple fragility fractures in 2012, has not incurred further fractures following the commencement of denosumab. Key learning points Denosumab has shown satisfactory improvement in these patients without significant adverse effects, following completion of 10 years of therapy. This is in par with previous studies that demonstrated efficacy and safety profile of Denosumab.

OA10 Pregnancy-associated osteoporosis - a rare subset of bone disease

OA10 Pregnancy-associated osteoporosis - a rare subset of bone disease

Identification of mouse soleus muscle proteins altered in response to changes in gravity loading

Gravity-dependent physical processes strongly affect the ability of elderly people to maintain musculoskeletal health by reducing muscle atrophy and increasing bone mineral density, thereby increasing quality of life. A need therefore exists to identify molecules in the musculoskeletal system that are responsive to gravitational loading and to establish an objective indicator for the maintenance of healthy musculoskeletal systems. Here, we performed an integrated assessment of the results of soleus muscle proteomic analyses in three model mouse experiments under different gravity environments (hypergravity, hindlimb unloading, and spaceflight). Myl6b, Gpd1, Fbp2, Pvalb, and Actn3 were shown to be gravity-responsive muscle proteins, and alterations in the levels of these proteins indicated changes in muscle fiber type to slow-twitch type due to gravity loading. In addition, immunoblotting and enzyme-linked immunosorbent assays revealed that Pvalb levels in the sera of hindlimb-unloaded mice and osteoporosis patients were higher than in control subjects, suggesting that Pvalb levels might be useful to objectively evaluate soleus muscle atrophy and bone loss.

Effect of Growth Hormone and Estrogen Replacement Therapy on Bone Mineral Density in Women with Turner Syndrome: A Meta-Analysis and Systematic Review.

Osteoporosis is a serious implication of Turner syndrome (TS). Common methods for the treatment of TS are growth hormone (GHT) and estrogen replacement therapy (ERT). We examined the relationship between the treatment of TS and bone mineral density (BMD) of the lumbar spine. The purpose of our study was to show the currency of BMD states among patients with TS for treatment with GHT and ERT. We searched databases for studies published from inception to April 2023. The articles were related to TS, osteoporosis, ERT, GHT, BMD and treatment patients with TS. We applied the selection criteria: lumbar spine values at L1-L4; dual-energy X-ray absorptiometry (DXA); treatment which was applied: one group of articles: ERT and two group of articles: GHT; results performed as means ± SD. In total, 79 articles were analyzed, of which 20 studies were included and 5 were considered for meta-analysis. The total number of women in the articles selected was 71. Based on the results of the meta-analysis, the effect of ERT on BMD demonstrated a significant increase in BMD (the standardized mean difference in the random model was 0.593 g/cm2, 95% CI: 0.0705 to 1.116; p = 0.026), which showed that treatment with estrogen particularly increases bone mass during treatment, which contributes to reducing the risk of fractures. The effect of GHT on BMD demonstrated a non-significant decrease in BMD in patients with TS. The results for growth hormone show that this therapy does not improve bone density. However, our review emphasizes the beneficial effect of supplementing growth hormone (GH) on the clinical presentation of TS.

Comparative Effectiveness of Therapeutic Interventions in Pregnancy and Lactation-Associated Osteoporosis: A Systematic Review and Meta-analysis.

The optimal management of pregnancy and lactation-associated osteoporosis (PLO) has not been designated. To systematically review the best available evidence regarding the effect of different therapeutic interventions on bone mineral density (BMD) and risk of fractures in these patients. A comprehensive search was conducted in PubMed/Scopus databases until December 20, 2022. Data were expressed as weighted mean difference (WMD) with 95% CI. The I2 index was employed for heterogeneity. Studies conducted in women with PLO who received any antiosteoporosis therapy were included. Studies including women with secondary causes of osteoporosis or with transient osteoporosis of the hip were excluded. Data extraction was independently completed by 2 researchers. Sixty-six studies were included in the qualitative analysis (n = 451 [follow-up time range 6-264 months; age range 19-42 years]). The increase in lumbar spine (LS) BMD with calcium/vitamin D (CaD), bisphosphonates, and teriparatide was 2.0% to 7.5%, 5.0% to 41.5%, and 8.0% to 24.4% at 12 months, and 11.0% to 12.2%, 10.2% to 171.9%, and 24.1% to 32.9% at 24 months, respectively. Femoral neck (FN) BMD increased by 6.1% with CaD, and by 0.7% to 18% and 8.4% to 18.6% with bisphosphonates and teriparatide (18-24 months), respectively. Meta-analysis was performed for 2 interventional studies only. Teriparatide induced a greater increase in LS and FN BMD than CaD (WMD 11.5%, 95% CI 4.9-18.0%, I2 50.9%, and 5.4%, 95% CI 1.2-9.6%, I2 8.1%, respectively). Due to high heterogeneity and lack of robust comparative data, no safe conclusions can be made regarding the optimal therapeutic intervention in women with PLO.

Effects of Different Intensity Exercises On Bone Structure of Young Male Wistar Rats

Many adolescents have insufficient physical activity. Regular physical activity from young age can improve health and fitness. Getting regular exercise and eating healthy diet should be encouraged among kids and teenagers to prevent various diseases in adulthood and old age, such as osteoporosis and fractures. When exercising, a prescription is needed that is tailored to each individual abilities. The intensity of exercise will be different for each individual in accordance with their age, physiological function, genetics, economic status, and previous comorbid diseases. There is no standardised exercise prescription proven to increase bone mineral density in adolescents. Based on the above description, a study was conducted on the provision of different intensity exercise and its effect on bone morphology and density. In this study, male Wistar rats, aged 15–16 weeks (body weight ± 250-350 grams; n = 20), were split into 4 groups, namely control group, low intensity exercise group, moderate intensity exercise group, and high intensity exercise group. All groups were receiving intervention for 8 weeks. Then, the rats were sacrificed and the femoral bones were isolated. Femur weight and femur length was checked. Bone density was examined using X-Ray and calculated by statistical tests. Research was conducted in the Central Laboratory, Universitas Padjadjaran. There were significant differences of femur weight between high intensity exercise group and control and low intensity exercise groups (p 0.05). Moderate and high intensity exercises significantly increased femur length as opposed to control and low intensity exercise groups (p 0.05). Bone density was higher in moderate and high intensity exercise groups (p 0.05). Moderate to high intensity exercise can increase bone health, seen from significances of bone morphology analysis and a higher density compared to low intensity exercise.

The Effect of Denosumab in Elderly Patients Regarding Bone Density and Fracture Risk.

With an aging population, the importance of treating and diagnosing osteoporosis is increasing. Osteoporosis, previously known as a resorptive change primarily related to endocrinological mechanisms, is also being approached as a phenomenon of senile change. Denosumab is gaining popularity among osteoporosis medications due to its ability to increase bone mineral density (BMD) and the economic benefit arising from the 6-month cycle. In line with previous literature, this study aimed to examine the BMD-augmenting effect of denosumab through which it reduces fracture risk in individuals aged over 80 years. We reviewed patients who received denosumab between 2018 and 2022 with a minimum clinical observation period of 12 months. BMD was measured every 12 months, and patients were classified per their period of denosumab use. Fracture risk was evaluated using the fracture risk assessment tool (FRAX) and fracture incidence during the observation period were assessed. Among 155 patients, a significant increase in BMD was observed at 3 sites: the lumbar spine, femoral neck, and total hip (p<0.001, p<0.001, and p=0.001, respectively). The patients were divided according to the length of clinical follow-up they received, and similar results were found in all subgroups. Fracture risk assessment was performed using FRAX and the incidence of fracture events during follow-up. FRAX significantly decreased in all subgroups except those who received 24 months of follow-up (p=0.003, p=0.41, p=0.001 in the 12, 24, and ≥36 months groups, respectively). Denosumab use resulted in long-term BMD increase and reduced fracture risk in individuals aged 80 and above.

A Cluster Analysis of Oral and Cognitive Health Indicators in the CLSA: An Exploratory Study on Cholinergic Activity as the Link.

Poor oral health has been suggested as a risk factor for cognitive decline. Yet, biologically plausible mechanisms explaining this relationship remain unknown. We aimed (1) to identify oral and cognitive health clustering patterns among middle-aged to elderly Canadians and (2) to investigate the extent to which these patterns could be explained by bone mineral density (BMD), a proxy measure of the cholinergic neurons' activity. This cross-sectional study used baseline data from the Comprehensive cohort of the Canadian Longitudinal Study of Aging (CLSA). Oral health was assessed by a self-report questionnaire, and 7 task-based instruments measured cognitive health. We identified oral and cognitive health clusters, our outcome variables, using latent class analysis. Two sets of multivariate logistic regression and 95% confidence intervals were used to investigate whether BMD explains the odds of membership in a certain oral and cognitive health group. The final models were adjusted for socioeconomic, health, and lifestyle factors. Our study sample (N = 25,444: 13,035 males, 12,409 females) was grouped into 5 and 4 clusters based on the oral health status and performance on the cognitive tasks, respectively. After adjusting for all potential covariates, increase in BMD was not associated with higher odds of membership in classes with better oral health (odds ratio [OR] = 1.58 [95% confidence interval {CI}: 0.85-2.92]) and cognitive health (OR = 1.61 [95% CI: 1-2.6]) compared with the groups with the least favorable oral and cognitive health status, respectively. Middle-aged and elderly Canadians show different oral and cognitive health profiles, based on their denture-wearing status and performance on cognitive tests. No evidence could be found to support BMD in place of cholinergic neurons' activity as the common explanatory factor behind the association between oral health and cognitive health. This study is probably the first of its kind to shed light on the cholinergic system as a potential pathway influencing oral and cognitive health. Our findings may support the notion that any potential association between poor oral health and cognitive health might be explained by common contributors, helping clinicians to find the common risk factors for both conditions.

Romosozumab is associated with greater trabecular bone score improvement compared to denosumab in postmenopausal osteoporosis.

Romosozumab significantly increases bone mineral density (BMD) and rapidly reduces fracture risk. Whether romosozumab can improve the spinal trabecular bone score (TBS) as a bone quality indicator merits further investigation. Data for postmenopausal women starting romosozumab or denosumab treatment at Severance Hospital, Korea, were analyzed. Romosozumab and denosumab groups were 1:1 matched using propensity scores, considering relevant covariates. Good responders were defined as those with TBS improvement of 5.8% or greater. Overall, 174 patients (romosozumab, n = 87; denosumab, n = 87) were analyzed. Matched groups did not differ in age (64years), weight, height, previous fracture (38%), lumbar spine or femoral neck BMD (T-score, -3.4 and -2.6, respectively), or prior bisphosphonate or selective estrogen receptor modulator (SERM) exposure (50%). The romosozumab group exhibited a greater increase in lumbar spine BMD (15.2% vs. 6.9%, p < 0.001) and TBS (3.7% vs. 1.7%, p = 0.013) than the denosumab group. In patients transitioning from bisphosphonate or SERM, romosozumab users showed greater improvement in TBS compared to denosumab users (3.9% versus 0.8%, P = 0.006); the drug-naive group showed no significant difference (3.6% versus 2.7%, P = 0.472). The romosozumab group had a higher proportion of good responders than the denosumab group (33.3% vs. 18.4%, p = 0.024). Romosozumab therapy for 12months resulted in 3.8-fold higher odds of a good response in TBS than denosumab after covariate adjustment (adjusted odds ratio 3.85, p = 0.002). Romosozumab could improve bone mass and bone quality, measured by TBS, in postmenopausal osteoporosis, particularly as a subsequent regimen in patients previously taking anti-resorptive agents.

The Effects of Whole-Body Vibration Training on Trunk Muscle Strength: A Narrative Review

Mechanical vibration can improve neuromuscular function through postural control strategies, muscle tonic mechanisms, and tonic vibration reflexes. Whole body vibration (WBV) has also been announced to increase bone mineral density, muscle endurance and strength, as well as to enhance proprioceptive system. Moreover, WBV training was found to be a constructivestrategy for improving the physical performance of elite athletes and healthy individuals in terms of muscle strength, agility, flexibility, and vertical jump height. Although there is still no consensus in research in this area, it is argued that certainmolecular mechanisms involved in the physiological adaptations of exercise also emerge during WBV training. Clarifying these physiological mechanisms is crucial for optimizing the effectiveness of WBV trainings. Previous studies have examined the effects of WBV and have indicated developments in muscle strength, muscle endurance, flexibility, muscle cross sectional area, bone mineral density and body composition. However, no standard prescription has been established to optimize the effects of WBV, including the determination of vibration frequency and amplitude. In addition, the majority of previous studies have investigated the effects of WBV training on the extremities. There are few publications investigating its effectiveness on trunk and core musclestrength, which is one of the important indicators of athletic performance. Therefore, we conducted a narrative review of the literature, referring to the Cochrane Library and Medline databases, to summarize the most recent scientific evidence on the effects of whole-body vibration on trunk muscle strength. This narrative review concludes that at least 8 weeks of WBV training is more effective on trunk muscle strength than those performing the same exercises without WBV.

Endocortical Trabecularization in Acromegaly: The Cause for the Paradoxically Increased Vertebral Fracture Risk?

Growth hormone (GH) is nonphysiologically increased in acromegaly, stimulating target tissues directly and indirectly via insulin-like growth factor type 1 (IGF-1). Despite GH having anabolic effects on bone growth and renewal, the risk of vertebral fractures is paradoxically increased in acromegaly. We hypothesized that bone tissue compartments were differentially affected by hormonal alterations in active and controlled acromegaly. We aimed to study the effect of sex and gonadal status on long-term outcome of bone mass and structure to understand the biomechanical competence of bone. We followed 62 patients with newly diagnosed acromegaly longitudinally (median 4.8 years after pituitary surgery) to investigate changes assessed by dual X-ray absorptiometry (DXA), trabecular bone score (TBS), and hip structure analysis (HSA). At diagnosis, patients had increased bone mineral density (BMD) in most compartments compared with normative data (Z-scores). Conversely, TBS Z-score was decreased (Z = -0.64 (SD 1.73), p = 0.028). Following treatment of acromegaly, BMD increased further in compartments containing predominantly trabecular bone, such as the lumbar spine, in eugonadal and male subjects, while compartments with predominantly cortical bone, such as the hip and femoral neck, were unchanged. Total body measurements showed further increase in BMD independent of sex and gonadal status. TBS did not change. HSA revealed a significant decrease in cortical thickness in both sexes independent of gonadal status, whereas the overall size of bone (hip axis length and neck width) did not change over time. In conclusion, patients with acromegaly had increased bone mass and dimensions by DXA. Following normalization of disease activity, BMD increased mainly in compartments rich in trabecular bone, reflecting a closure of the remodeling space. However, HSA revealed a significant decrease in cortical thickness, implying endocortical trabecularization, potentially explaining the increased risk for incident vertebral fractures following treatment. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

The effects of selenium on the growth and bone development in the weaned rats

Selenium is a crucial trace element, and a deficiency of selenium can cause oxidative stress damage and impede the growth and development of the body. L-Se-methylselenocysteine (L-SeMC) is a naturally occurring organic-selenium, which has higher bioavailability compared to inorganic-selenium such as Na2SeO3. In this study, weaned rats were fed with a selenium-deficient liquid diet to simulate the selenium-deficient breastfeeding. High and low doses of Se were supplemented in the liquid feed with L-SeMC and Na2SeO3, respectively. The results showed that the selenium-deficient diet reduced the growth rate and development of the weaned rats, leading to oxidative stress in the body and damaging liver and kidney function, as well as causing the histological lesions in heart and knee joints. Supplementing high doses (0.20 mg Se/kg) of L-SeMC and Na2SeO3 could increase the body weight of selenium-deficient rats by 10.48% and 4.47%, respectively. The symptoms caused by selenium deficiency were significantly relieved after supplementation with selenium, with L-SeMC being more effective than Na2SeO3. Furthermore, femoral bone mineral density (BMD) was increased by 77.0% with supplementation of L-SeMC in the selenium-deficient rats, while supplementation with Na2SeO3 resulted in only a 19.4% increase in BMD. These findings indicated that due to its higher bioavailability and superior ability to alleviate oxidative stress damage and growth retardation caused by selenium deficiency, L-SeMC is a better supplement for alleviating the oxidative stress and liver and kidney damage caused by selenium deficiency, and has a superior therapeutic effect on myocardial tissue and knee joint lesions compared to Na2SeO3.