Increase In BMD Research Articles

Bone density changes in young women in Uganda using tenofovir-based HIV pre-exposure prophylaxis and depot medroxyprogesterone acetate contraception

Background: Injectable depot medroxyprogesterone acetate (DMPA) is the most common contraceptive choice among young women in Uganda, where HIV burden is high and HIV pre-exposure prophylaxis (PrEP) may be offered. For young women who choose to use both agents concurrently, it is unknown whether they will experience declines in BMD beyond those elicited by either product singly. Methods: From 2018–2022, we conducted a 2-year prospective study with women ages 16–25 years in Kampala, Uganda desiring pregnancy and HIV prevention. Women were provided condoms, injectable DMPA, and/or FTC/TDF, according to their choices and underwent annual dual x-ray absorptiometry (DXA) scans. We used tenofovir-diphosphate (TFV-DP) quantification in dried blood spots and DMPA injection dates to classify exposure. Linear regression models estimated the difference in % BMD change from baseline to month 12 for women using FTC/TDF and DMPA versus women using neither product. Results: Of 499 enrolled women, discontinuation and re-starting of contraception and PrEP was common. Women consistently using neither product (n = 39) experienced BMD increases. Women with consistent use of both products during 1 year (n = 22) experienced an average BMD loss of 1.04% at lumbar spine and hip and 1.77% at femoral neck. These losses were different relative to women who used neither agent: lumbar spine -3.35% (95% CI −5.13%, −1.56%, p = 0.001), total hip −2.24% (95% CI −3.87%, −0.60%, p = 0.009), and femoral neck −1.71% (95% CI −3.73%, 0.31%, p = 0.102). Conclusion: We observed a trend for women with concurrent DMPA and FTC/TDF PrEP use to have 1–3% lower BMD than unexposed women after 12 months.

7740 Adult-Onset Hypophosphatasia Presenting As Low Alkaline Phosphatase Level Following Denosumab Use For Osteoporosis

Abstract Disclosure: J. Ocampo Mascaro: None. P. Wax: None. M. Al Mukaddam: Grant Recipient; Self; Ipsen, Incyte Research Funding. Background: Hypophosphatasia (HPP) is a genetic disease characterized by low activity of the tissue non-specific alkaline phosphatase. It has a broad range of clinical phenotypes, with adults usually presenting with an incidental low alkaline phosphatase (ALP) finding. Differentiating this from other causes of low ALP is challenging, especially when treating osteoporosis, as antiresorptive therapy such as denosumab and bisphosphonates may cause low ALP and carry the potential of increasing risk of atypical femoral fractures in patients with undiagnosed HPP. Clinical Case: A 64-year-old woman with history of nephrolithiasis, hypercalciuria, and osteoporosis (screening DXA lowest T-score -3.3 in femoral neck (FN)) but no prior fractures or dental issues was seen in clinic. Initial bloodwork showed normal range calcium, 25-OH vitamin D, and intact PTH. Pre-treatment ALP was 42 IU/L (N 39-117). Work up for secondary causes of osteoporosis was negative. Three yearly doses of IV zoledronic acid resulted in +4.2% BMD increase in lumbar spine (LS) but no changes in FN. She had no side effects but was found to have a decrease in ALP to 33 IU/L. This normalized back to 42 IU/L during a three-year drug holiday. Follow up DXA noted significant decline in BMD, hence denosumab was initiated. ALP decreased back to the 30-35 IU/L range. Fasting Vitamin B6 level (off B6 supplements for 1 week) was 23.4 ng/ml (N 2.1-21). Urine phosphoethanolamine was mildly elevated at 5 mmol/mol creatinine (N ≤4). Genetic testing evidenced a pathogenic ALPL variant (Exon 6, c.575T>C (p.Met192Thr), heterozygous) compatible with HPP. She had tolerated three doses of denosumab by then with BMD improvement of 5.0% in LS but no changes in FN and no atypical femoral fracture. Denosumab was stopped. Abaloparatide was started for osteoporosis with close monitoring for worsening hypercalciuria. Conclusion: This case demonstrates that adult HPP patients may present with subtle findings and lower range of normal ALP and may tolerate short courses of antiresorptive agents. There is a need for better screening and diagnostic criteria for adult HPP patients whose ALP levels may not be initially low before initiating antiresorptive drugs for osteoporosis. The risk of adverse effects from therapy will likely vary significantly based on the clinical severity/presentation of HPP as some adults with lower ALP ranges might be more susceptible to developing atypical femur fractures (1). Balancing atypical femur fracture risk with the benefits of antiresorptive treatment in decreasing risk of osteoporotic fractures highlights the need for better risk stratification to prevent undertreatment of osteoporosis. Reference: 1. Warren AM, Ebeling PR, Grill V, Seeman E, Sztal-Mazer S. Bilateral atypical femoral fractures during denosumab therapy in a patient with adult-onset hypophosphatasia. Endocrinol Diabetes Metab Case Rep. 2021 Sep 1;2021:21-0096. Presentation: 6/2/2024

Growth and physical development of children at apparent risk of sarcopenia.

The consequences of sarcopenia on growth have received little attention. We analysed the potential risk resulting from the low lean mass for age expressed through the appendicular lean body mass index (aLBMI) and the ratio aLBM/trunk fat mass (trFM). The sample consisted of 580 participants 10-13 yrs evaluated twice in a 12-month interval: height, trFM, total and aLBM, whole-body bone mineral density less head (WBLH BMD), tibia and radius SOS, maturity and handgrip strength were measured. All variables except maturity and BMI were standardised according to sex and age group (Z-score) using the sample as a reference. A high risk of sarcopenia was identified for Z-scores ≤ -1 on aLBMI (Group B) or aLBM/trFM (Group C), while Z-scores > -1 on both markers were considered at low risk for sarcopenia (Group A). The ANCOVA adjusted for maturity was used to compare the three groups. Girls showed a more significant decrease in the total BMC/LBM ratio in Group B and a minor increase in WBLH BMD in Group C (p < 0.050); boys in Group B showed a tendency to gain less height (p = 0.053). The high risk of sarcopenia expressed through aLBMI or aLBM/trFM Z-score ≤ -1 compromises bone mineralisation in girls. The findings emphasise the necessity of implementing routine screening protocols for sarcopenia risk within clinical environments and educational institutions. Such screenings should extend beyond merely assessing body mass index to encompass broader body composition variables like lean body mass. By integrating these assessments into routine health evaluations, healthcare professionals and educators can proactively identify at-risk individuals and initiate timely interventions for suboptimal physical growth and development.

Effective strategies for pregnancy and lactation-associated osteoporosis: teriparatide use in focus.

Pregnancy and lactation-associated osteoporosis (PLO) is a rare condition characterized by fragility fractures occurring during late pregnancy or lactation, primarily affecting the spine and causing significant morbidity and back pain. PLO can lead to mobility impairment and work incapacity, with recovery taking up to several years. Due to the lack of clinical trials, treatment strategies remain poorly defined, historically focusing on calcium supplements, vitamin D, and weaning from breastfeeding. However, recent attention has turned to teriparatide (TPD) as an option due to its anabolic properties and potential suitability for women of childbearing age. This review evaluates TPD's use in PLO treatment, using published systematic reviews and case studies. Over 300 cases with PLO were identified through PubMed, Google Scholar, and Cochrane searches until August 2023. We identified 175 cases with PLO treated with TPD alone or followed by antiresorptive therapy. Most women (85.7%) were primiparas. The mean ± SD duration of TPD use was 15 ± 6 months. Among the study patients, 91.4% used TPD alone, while 8.6% (15/175) utilized sequential therapy. Approximately 93% of our cohort exhibited potential risk factors for PLO. Despite the increased risk of recurrent fractures in PLO, only 14.7% (20/175) of those treated with TPD sustained new fractures during a 9-month to 9 years' follow-up period. The mean ± SD percent increase in BMD at the LS was 21.14% ± 7.4%, and at the FN it was 12.1% ± 9.3%. The baseline Z-scores at the LS ranged from -3.3 (-3.7 to -2.7), while the baseline Z-scores at the FN ranged from -2.0 (-2.7 to -1.5). This review emphasizes PLO severity, advocating for increased awareness and timely interventions. TPD emerges as a promising therapeutic option in certain cases.

Hypogonadism as a consequence of craniopharyngioma in female patients: comparison of childhood and adult onset and effects of estrogen replacement therapy.

(1) to compare clinical, biochemical features in female patients with hypoestrogenism due to childhood- and adult-onset CP; (2) to reveal effects of estrogen replacement therapy in female patients with childhood-onset CP. Thirty-seven women that received specific treatment for CP in the period from 1980 to 2019 were recruited: 21 with childhood-onset and 16 with adult-onset CP. Clinical and hormonal characteristics were evaluated. Seventeen-beta-estradiol 2 mg and dydrogesterone 10 mg in sequential regiment was used in 18 childhood-onset cases. Mean follow-up was 31 months. Amenorrheic women with childhood- and adult-onset CP presented with the same complaints except for lack of genital hair and breast hypoplasia, which were common in patients with childhood-onset CP. BMI was lower in childhood-onset CP group, as was the proportion of overweight patients. They had more favorable lipid profile. The levels of estradiol, testosterone and DHEA-S were low and did not differ. Uterine and ovary volumes were reduced in all patients, but the decline was noticeable in the childhood-onset group. Mineral bone density of lumbar vertebrae was diminished in childhood-onset group. Estrogen therapy in these patients led to clinical improvement: increase in BMD in lumbar spine without negative changes in BMI and/or lipid profile. Study showed that women with childhood-onset CP had less negative metabolic changes. However, they have more pronounced breast and uterus hypoplasia and lower BMD in lumbar spine. The estrogen replacement therapy led to clinical improvement and BMD increase in lumbar spine without increase of BMI and/or lipid profile changes.

Influence of age on the efficacy of pharmacologic treatments on fracture risk reduction and increases in BMD: RCT results from the FNIH-ASBMR-SABRE project.

There is a common belief that antiosteoporosis medications are less effective in older adults. This study used data from randomized controlled trials (RCTs) to determine whether the anti-fracture efficacy of treatments and their effects on BMD differ in people ≥70 compared to those <70yr. We used individual patient data from 23 RCTs of osteoporosis medications collected as part of the FNIH-ASBMR SABRE project. We assessed the following fractures: radiographic vertebral, non-vertebral, hip, all clinical, and all fractures. We used Cox proportional hazard regression to estimate treatment effect for clinical fracture outcomes, logistic regression for the radiographic vertebral fracture outcome, and linear regression to estimate treatment effect on 24-mo change in hip and spine BMD in each age subgroup. The analysis included 123 164 (99% female) participants; 43% being ≥70yr. Treatment with anti-osteoporosis drugs significantly and similarly reduced fractures in both subgroups (eg, odds ratio [OR] = 0.47 and 0.51 for vertebral fractures in those below and above 70yr, interaction P = .19; hazard ratio [HR] for all fractures: 0.72 vs 0.70, interaction P = .20). Results were similar when limited to bisphosphonate trials with the exception of hip fracture risk reduction which was somewhat greater in those <70 (HR = 0.44) vs ≥70 (HR = 0.79) yr (interaction P = .02). Allocation to anti-osteoporotic drugs resulted in significantly greater increases in hip and spine BMD at 24mo in those ≥70 compared to those <70yr. In summary, anti-osteoporotic medications similarly reduced the risk of fractures regardless of age, and the few small differences in fracture risk reduction by age were of uncertain clinical significance.

New Perspectives of Therapies in Osteogenesis Imperfecta-A Literature Review.

(1) Background: Osteogenesis imperfecta (OI) is a rare skeletal dysplasia characterized as a heterogeneous disorder group with well-defined phenotypic and genetic features that share uncommon bone fragility. The current treatment options, medical and orthopedic, are limited and not efficient enough to improve the low bone density, bone fragility, growth, and mobility of the affected individuals, creating the need for alternative therapeutic agents. (2) Methods: We searched the medical database to find papers regarding treatments for OI other than conventional ones. We included 45 publications. (3) Results: In reviewing the literature, eight new potential therapies for OI were identified, proving promising results in cells and animal models or in human practice, but further research is still needed. Bone marrow transplantation is a promising therapy in mice, adults, and children, decreasing the fracture rate with a beneficial effect on structural bone proprieties. Anti-RANKL antibodies generated controversial results related to the therapy schedule, from no change in the fracture rate to improvement in the bone mineral density resorption markers and bone formation, but with adverse effects related to hypercalcemia. Sclerostin inhibitors in murine models demonstrated an increase in the bone formation rate and trabecular cortical bone mass, and a few human studies showed an increase in biomarkers and BMD and the downregulation of resorption markers. Recombinant human parathormone and TGF-β generated good results in human studies by increasing BMD, depending on the type of OI. Gene therapy, 4-phenylbutiric acid, and inhibition of eIF2α phosphatase enzymes have only been studied in cell cultures and animal models, with promising results. (4) Conclusions: This paper focuses on eight potential therapies for OI, but there is not yet enough data for a new, generally accepted treatment. Most of them showed promising results, but further research is needed, especially in the pediatric field.

Romosozumab added to ongoing denosumab in postmenopausal osteoporosis, a prospective observational study.

Optimization of sequential and combination treatment is crucial in shaping long-term management of postmenopausal osteoporosis (OP). We conducted a 6-month prospective observational study on postmenopausal women with severe OP receiving treatment with romosozumab either alone (in patients naïve to treatment) or in combination with ongoing long-term denosumab (>2years) or continuing ongoing denosumab alone (>2years). We collected serum samples for bone turnover markers, bone modulators, and calcium phosphate metabolism at baseline, month 3 and month 6. BMD was assessed at baseline and after 6months. Fifty-two postmenopausal women with OP were included in the study. Nineteen received romosozumab alone, 11 received romosozumab combined to ongoing denosumab, and 22 continued denosumab alone. BMD increased significantly at all sites at 6months of follow-up in the romosozumab alone group (femoral neck +8.1%, total hip +6.8%, and lumbar spine +7.9%). In contrast, BMD increased significantly only at lumbar spine in the combination group (+7.2%) and in the denosumab group (+1.5%). P1nP increased significantly in romosozumab groups at month 3 (+70.4% in romosozumab alone group and +99.1% in combination group). Sclerostin levels increased steeply in both romosozumab groups, and Dkk1 did not change. Romosozumab added to ongoing denosumab resulted in an increase in P1nP and lumbar spine BMD, but not in femoral neck BMD. For patients on denosumab, using romosozumab as an additional treatment appeared to be useful in terms of bone formation markers and spine BMD vs denosumab alone. Further randomized controlled trials, possibly powered to fracture outcomes, are needed to confirm our results.

Response rates for lumbar spine, total hip, and femoral neck bone mineral density in men treated with abaloparatide: results from the ATOM study.

Osteoporosis in men is an underappreciated public health issue, accounting for approximately 30% of the societal burden of osteoporosis. Although the prevalence of osteoporosis in men is lower, fracture-related morbidity and mortality rates exceed those of women. Abaloparatide is a synthetic, 34-amino acid peptide with homology to human parathyroid hormone-related protein (PTHrP), which favors bone formation by selective activation of PTH receptor type 1. In the Abaloparatide for the Treatment of Men With Osteoporosis (ATOM; NCT03512262) trial, 228 men with primary or hypogonadism-associated osteoporosis were randomized to receive subcutaneous injections of abaloparatide 80μg or placebo. Abaloparatide significantly improved LS, TH, and FN BMD when compared with placebo. In this prespecified analysis, the proportion of men with a percent change from baseline of >0%, >3%, and > 6% in BMD at the LS, TH, and FN at 3, 6, and 12mo and/or a shift in T-score category (based on LS and TH T-scores) at 12mo was compared between the abaloparatide and placebo groups in ATOM. There were significantly more men with a BMD gain of >3% at all 3 anatomical sites in the abaloparatide than placebo group at month 6 (18/122 [14.8%] vs 1/70 [1.4%], P = .002) and at month 12 (38/119 [31.9%] vs 1/66 [1.5%], P < .0001). At month 3, more men treated with abaloparatide than placebo had a > 3% BMD increase at the LS (82/134 [61.2%] vs 21/68 [30.9%], P < .0001). A greater proportion of men treated with abaloparatide had an improvement in T-score category from osteoporosis to low BMD or normal when compared with placebo. In conclusion, use of abaloparatide compared with placebo for 12mo resulted in significant and rapid improvements in BMD in men with osteoporosis from the ATOM study.

Sex-specific effects of Fat-1 transgene on bone material properties, size, and shape in mice.

Western diets are becoming increasingly common around the world. Western diets have high omega 6 (ω-6) and omega 3 (ω-3) fatty acids and are linked to bone loss in humans and animals. Dietary fats are not created equal; therefore, it is vital to understand the effects of specific dietary fats on bone. We aimed to determine how altering the endogenous ratios of ω-6:ω-3 fatty acids impacts bone accrual, strength, and fracture toughness. To accomplish this, we used the Fat-1 transgenic mice, which carry a gene responsible for encoding a ω-3 fatty acid desaturase that converts ω-6 to ω-3 fatty acids. Male and female Fat-1 positive mice (Fat-1) and Fat-1 negative littermates (WT) were given either a high-fat diet (HFD) or low-fat diet (LFD) at 4wk of age for 16wk. The Fat-1 transgene reduced fracture toughness in males. Additionally, male BMD, measured from DXA, decreased over the diet duration for HFD mice. In males, neither HFD feeding nor the presence of the Fat-1 transgene impacted cortical geometry, trabecular architecture, or whole-bone flexural properties, as detected by main group effects. In females, Fat-1-LFD mice experienced increases in BMD compared to WT-LFD mice; however, cortical area, distal femur trabecular thickness, and cortical stiffness were reduced in Fat-1 mice compared to pooled WT controls. However, reductions in stiffness were caused by a decrease in bone size and were not driven by changes in material properties. Together, these results demonstrate that the endogenous ω-6:ω-3 fatty acid ratio influences bone material properties in a sex-dependent manner. In addition, Fat-1 mediated fatty acid conversion was not able to mitigate the adverse effects of HFD on bone strength and accrual.

The Effects of Switch Therapy in Osteoporosis Treatment after Romosozumab after Comparing with Prior Treatment.

Rationale. Although romosozumab is one of the most effective treatments for osteoporosis by increasing bone mineral density in the lumbar spine and femur and recommended for denosumab as switch therapy, these effects regarding its prior treatment have not yet been evaluated clearly. This study focused on the effects of switch therapy from romosozumab to denosumab in regard to prior treatment of osteoporosis including bone mineral density and bone turnover marker and other related factors. Patient Concerns. 15 osteoporotic patients were assigned to the naïve group, 15 were assigned to the teriparatide group, and 10 were assigned to the bisphosphonate group. Interventions. Patients who were treated as outpatients for osteoporosis with romosozumab for 1 year and switched to denosumab between 2020 and 2022 at our hospital were examined. Our hospital registry included 40 osteoporotic patients who were over 65 years of age with bone mineral density (bone mineral density): T score <-2.5 standard deviations (SDs) and fracture assessment tool (FRAX) score >20%. Outcomes. The naïve group had the highest increase in LS BMD among these three groups during switch therapy from romosozumab to denosumab, while there were no significant differences about adverse drug events and serum Ca concentration among them. There was no incidence of fracture. Conclusion. These findings indicate that the effects of osteoporotic treatment of switch therapy from romosozumab to denosumab were likely to affect prior treatment of osteoporosis.

Analysis of the efficacy of drilling decompression autologous bone marrow and allogeneic bone grafting in the treatment of HIV-positive patients with early osteonecrosis of the femoral head

ObjectiveTo investigate the efficacy of treating patients with HIV-positive osteonecrosis of the femoral head using drilled decompression autologous bone marrow and allogeneic bone grafting.Methods40 patients (44 hips) with early osteonecrosis of the femoral head treated by drilling decompression autologous bone marrow and allogeneic bone grafting since October 2015 were retrospectively analyzed, among which 20 patients (24 hips) were HIV-positive patients with early osteonecrosis of the femoral head, 16 males and 4 females, age 22–43 years, average 39.6 ± 10.18 years, and 20 patients (20 hips) in the same period HIV-negative early osteonecrosis of the femoral head patients, 13 males and 7 females, aged 48–78 years, mean 63.50 ± 7.94 years were negative controls. General information including ARCO stage, Harris score, VAS score, hematological indexes including CD4+ T lymphocyte count, and HIV viral load was recorded for all patients before surgery. All patients were operated on by drilling and decompression of the necrotic area, harvesting autologous iliac bone marrow with allogeneic bone, and bone grafting through the decompression channel. The patients were followed up regularly at 6, 12, and 24 months after surgery and annually thereafter, and the repair of the necrotic femoral head was observed by reviewing the frontal and lateral X-ray, CT or MRI of the hip joint, and the complications and functional recovery of the hip joint was counted and compared between the two groups.ResultsAll patients were followed up, and the ARCO stages in the HIV-positive group were stage I 2 hips, stage IIA 6 hips, stage IIB 8 hips, stage IIC 6 hips, and stage III 2 hips, with a follow-up time of 12 to 60 months and a mean of 24.6 months. In the negative control group, there were 3 hips in ARCO stage I, 7 hips in stage IIA, 5 hips in stage IIB, 3 hips in stage IIC, and 2 hips in stage III, and the follow-up time ranged from 13 to 62 months, with an average of 24.8 months. The Harris score and VAS score of the hip in both groups improved significantly at 6 months postoperatively compared with those before surgery (P < 0.001). The difference between the Harris score of the hip in the positive group at 24 months postoperatively compared with that at 6 months postoperatively was statistically significant, but the VAS score at 24 months postoperatively compared with that at 6 months postoperatively was not statistically significant. In the negative group, there was no statistically significant difference in the Harris score and VAS score of the hip at 24 months postoperatively compared with those at 6 months postoperatively. In the positive group, there was a trend of continuous increase in hip BMD from the beginning of the postoperative period (P < 0.001). There was no statistically significant difference between the negative group and the positive group at the 24 months postoperatively follow-up except for the Harris score, which was statistically significant (P < 0.001), and the VAS score, which was statistically insignificant. At the 24 months postoperatively follow-up, patients in both groups had good recovery of hip function, and no complications such as vascular and nerve injury and fracture occurred during the perioperative period and follow-up period, and no complications related to incisional infection and pulmonary infection occurred during hospitalization.ConclusionThe treatment of early HIV-positive osteonecrosis of the femoral head patients with autologous bone marrow and allogeneic bone grafting by drilling and decompression to remove the tissue in the necrotic area of the femoral head can effectively stop the process of osteonecrosis of the femoral head and promoting femoral head repair in HIV-positive patients is a safe and effective method for treating HIV-positive patients with early osteonecrosis of the femoral head, and can effectively delay or postpone total hip replacement in patients.

WITHDRAWN: Analysis of the Efficacy of Drilling Decompression Autologous Bone Marrow and Allogeneic Bone Grafting in the Treatment of HIV-positive Patients with Early Osteonecrosis of the Femoral Head

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Genetic interactions between polycystin-1 and Wwtr1 in osteoblasts define a novel mechanosensing mechanism regulating bone formation in mice

Molecular mechanisms transducing physical forces in the bone microenvironment to regulate bone mass are poorly understood. Here, we used mouse genetics, mechanical loading, and pharmacological approaches to test the possibility that polycystin-1 and Wwtr1 have interdependent mechanosensing functions in osteoblasts. We created and compared the skeletal phenotypes of control Pkd1flox/+;Wwtr1flox/+, Pkd1Oc-cKO, Wwtr1Oc-cKO, and Pkd1/Wwtr1Oc-cKO mice to investigate genetic interactions. Consistent with an interaction between polycystins and Wwtr1 in bone in vivo, Pkd1/Wwtr1Oc-cKO mice exhibited greater reductions of BMD and periosteal MAR than either Wwtr1Oc-cKO or Pkd1Oc-cKO mice. Micro-CT 3D image analysis indicated that the reduction in bone mass was due to greater loss in both trabecular bone volume and cortical bone thickness in Pkd1/Wwtr1Oc-cKO mice compared to either Pkd1Oc-cKO or Wwtr1Oc-cKO mice. Pkd1/Wwtr1Oc-cKO mice also displayed additive reductions in mechanosensing and osteogenic gene expression profiles in bone compared to Pkd1Oc-cKO or Wwtr1Oc-cKO mice. Moreover, we found that Pkd1/Wwtr1Oc-cKO mice exhibited impaired responses to tibia mechanical loading in vivo and attenuation of load-induced mechanosensing gene expression compared to control mice. Finally, control mice treated with a small molecule mechanomimetic, MS2 that activates the polycystin complex resulted in marked increases in femoral BMD and periosteal MAR compared to vehicle control. In contrast, Pkd1/Wwtr1Oc-cKO mice were resistant to the anabolic effects of MS2. These findings suggest that PC1 and Wwtr1 form an anabolic mechanotransduction signaling complex that mediates mechanical loading responses and serves as a potential novel therapeutic target for treating osteoporosis.

FRI683 Every Dose Counts: Response To Half The Recommended Dose Of Romosozumab

Abstract Disclosure: B.P. Ramchandani: None. F.S. Mirza: None. Introduction: Romosozumab (RSB) is a monoclonal antibody that inhibits sclerostin, increases bone formation and decreases bone resorption. It was approved by FDA in 2019 at a dose of 210 mg monthly for 1 year, followed by an anti-resorptive medication. We present a case of a 76 y.o. female with severe osteoporosis and history of intolerance to multiple medications, who was given half the monthly recommended dose of Romo due to extreme concern about side effects. We hereby report the response of her bone density to the treatment. Case Description: A 76-year-old female with history of primary biliary cirrhosis, Sjogren’s syndrome, hemorrhagic duodenal ulcer, s/p subtotal gastrectomy in 1962 presented for evaluation of severe osteoporosis. Fracture history was significant for T11 compression fracture in 2020 requiring kyphoplasty, and a T10 inferior endplate compression fracture requiring vertebroplasty in 2022. Osteoporosis was first diagnosed in 2005. She was intolerant of teriparatide in 2005 (stopped after six months due to nausea, hypercalcemia, cramps, pain in extremities and fatigue). Zoledronic acid (ZA) was administered in 2006 and 2008. Baseline urine telopeptide cross-links (NTx) was low at 18 which decreased to 10 while on ZA and further infusions were held. She declined denosumab and teriparatide was tried again in 2013 that she did not tolerate. She received ZA again in 2016. BMD did not improve on ZA and she declined further infusions. She was physically active and walked daily and was taking calcium citrate, vitamin D and ursodiol during this time. On examination, she was frail and elderly, with BMI of 16.6 mg/kg2. She had mild kyphoscoliosis of the spine with no spinal or paraspinal tenderness. Remainder of the exam was unremarkable. Laboratory evaluation showed normal serum calcium (9.5 mg/dl), albumin (4.1g/dl), Vit D 25-OH (36 mg/ml), bone specific alkaline phosphatase of 22.7 U/L and urine NTx of 23 nm BCE/mm creatinine. Bone density (BMD) in January 2022 showed lumbar spine (LS) BMD of 0.613 g/cm2 (T-score −4.7) and a total hip BMD of 0.575 g/cm2 (T-score −3.4). She was reluctant to consider any medications due to concern about side effects, but finally agreed to a trial of RSB at half the recommended dose at 105 mg monthly for 12 months. DXA scan a year later showed 17% increase in LS BMD (0.715 g/cm2, T-score -3.9), with stable total hip BMD. She has been transitioned to denosumab, which she was now agreeable to take. Discussion: Our patient showed significant improvement in BMD with half the recommended dose of RSB, comparable to the increase in LS BMD reported in phase 3 trials. She was petite and her weight-based dose was just short of 3 mg/kg body weight. Phase 1 and 2 studies had tried weight based and smaller doses of Romo and showed improvement in BMD. This case highlights the need for additional studies with weight-based dosing of RSB, which may reduce the cost of treatment. Presentation: Friday, June 16, 2023

THU438 A Case Of Pregnancy Associated Osteoporosis

Abstract Disclosure: S. Maradana: None. F. Iqbal: None. M. Safran: None. Background: Pregnancy associated osteoporosis (PAO) is a rare form of osteoporosis that is seen in late pregnancy and early post-partum period. Hip and vertebral body are most involved in PAO. Common clinical manifestation is back pain, and many patients suffer from vertebral fractures and kyphosis causing great physiologic burden and negative impact on quality of life. We report a case of PAO with good response to teriparatide. Clinical case: A 27-year-old female with no significant past medical history presented with severe acute back pain two months after delivery of her second child, whilst still breast feeding. Imaging studies demonstrated acute compression fractures of T12, L1, L2 and L3 vertebrae. She had regular monthly menstrual cycles prior to pregnancy with no previous history of fractures. Her pre pregnancy weight was 135 lbs and she had been physically active, while caring for her older son. Family history is notable for osteoporosis in multiple paternal aunts and maternal grandmother with no family history of fractures. There were no other identifiable risk factors. Evaluation for secondary causes of osteoporosis showed 25-OH vitamin D levels of 23 ng/mL (NL 30-100 ng/mL), TSH 1.72 uIU/mL (NL 0.28-3.8 uIU/mL), PTH 19 pg/mL (NL 14-64 pg/mL), calcium 9.7 mg/dL (NL 8.7-10.7 mg/dL), phosphorus 4 mg/dL (NL 2.5-4.5 mg/dL), tryptase 4 mcg/L (NL &amp;lt;11 mcg/L), alkaline phosphatase 111 U/L (NL 30-115 U/L) and 24-hour urine calcium 168 mg (NL 100-300 mg). Urine immune electrophoresis and serum immunofixation did not show any evidence of monoclonal gammopathy. DEXA scan showed low BMD with Z-score of −4.4 SD in lumbar spine -3.1 in femoral neck. She was diagnosed with PAO. She stopped breast feeding after the diagnosis. As the bone mineral density was very low, she was started on teriparatide along with calcium and vitamin D supplementation. One year after treatment initiation, her DEXA scan showed improved bone mineral density with Z-score of −3.5 in lumbar spine and −1.9 in femoral neck. Her osteoporosis is currently being managed with teriparatide with plan to continue for a total duration of 24 months. Conclusion: PAO is under-recognized and under-reported, with limited available evidence on the management. Spontaneous improvement in BMD is known to occur in 6-12 months after pregnancy and lactation have been completed, although, the addition of anti-resorptive treatment in this setting may result in superior BMD gain compared with calcium and vitamin D supplementation alone. Use of teriparatide has shown to have significant increase in BMD and help with pain relief in PAO. Teriparatide has helped with improving the BMD in our patient. Nevertheless, controlled trials are lacking, and the optimal timing of teriparatide use in these women remains uncertain. Presentation: Thursday, June 15, 2023

Correlation between bone mineral density and sarcopenia in US adults: a population-based study

IntroductionIn the aging process of the body, in addition to changes in fat and muscle content, there is also bone loss, implying the possibility of a strong muscle–bone–lipid link. In this study, we initially investigated the relationship between lumbar BMD and low muscle mass and the relationship between “muscle–bone–lipid.”MethodsThe datasets from the National Health and Nutrition Examination Survey (NHANES) 2011–2018 were used in a cross-sectional investigation. BMD and appendicular skeletal muscle (ASM) were measured by dual-energy X-ray absorptiometry (DXA), and appendicular skeletal muscle was adjusted by body mass index (BMI) as a marker of sarcopenia. Weighted multivariate regression and logistic regression analysis were used to explore the independent relationship between lumbar BMD and sarcopenia. Fitted smoothing curves and threshold effect analysis were used to describe the nonlinear relationship.ResultIn 8386 participants with ages 20–59 years, there was a negative association between lumbar BMD and sarcopenia. In the fully adjusted model, the risk of developing sarcopenia decreased by 93% for each 1-unit increase in lumbar BMD (OR = 0.07, 95%CI 0.03–0.20). The risk of sarcopenia was 58% lower in participants in the highest quartile of lumbar BMD than in those in the lowest quartile (OR = 0.42, 95%CI 0.27–0.64). This negative association was more pronounced in the population of women with BMI ≥ 25.ConclusionOur findings suggest that lumbar BMD is negatively associated with sarcopenia in US adults. The dynamic balance between “muscle–bone–lipid” is likely to be related to the pathogenesis of bone loss.

The Effects of n-3 PUFA Supplementation on Bone Metabolism Markers and Body Bone Mineral Density in Adults: A Systematic Review and Meta-Analysis of RCTs.

Supplemental n-3 polyunsaturated fatty acids (PUFA) on bone metabolism have yielded inconsistent results. This study aimed to examine the effects of n-3 PUFA supplementation on bone metabolism markers and bone mineral density through a meta-analysis of randomized controlled trials. A systematic literature search was conducted using the PubMed, Web of Science, and EBSCO databases, updated to 1 March 2023. The intervention effects were measured as standard mean differences (SMD) and mean differences (MD). Additionally, n-3 PUFA with the untreated control, placebo control, or lower-dose n-3 PUFA supplements were compared, respectively. Further, 19 randomized controlled trials (RCTs) (22 comparisons, n = 2546) showed that n-3 PUFA supplementation significantly increased blood n-3 PUFA (SMD: 2.612; 95% CI: 1.649 to 3.575). However, no significant effects were found on BMD, CTx-1, NTx-1, BAP, serum calcium, 25(OH)D, PTH, CRP, and IL-6. Subgroup analyses showed significant increases in femoral neck BMD in females (0.01, 95% CI: 0.01 to 0.02), people aged <60 years (0.01, 95% CI: 0.01 to 0.01), and those people in Eastern countries (0.02, 95% CI: 0.02 to 0.03), and for 25(OH)D in people aged ≥60 years (0.43, 95% CI: 0.11 to 0.74), treated with n-3 PUFA only (0.36, 95% CI: 0.06 to 0.66), and in studies lasting ≤6 months (0.29, 95% CI: 0.11 to 0.47). NTx-1 decreased in both genders (-9.66, 95% CI: -15.60 to -3.71), and serum calcium reduction was found in studies lasting >6 months (-0.19, 95% CI: -0.37 to -0.01). The present study demonstrated that n-3 PUFA supplementation might not have a significant effect on bone mineral density or bone metabolism markers, but have some potential benefits for younger postmenopausal subjects in the short term. Therefore, additional high-quality, long-term randomized controlled trials (RCTs) are warranted to fully elucidate the potential benefits of n-3 PUFA supplementation, as well as the combined supplementation of n-3 PUFA, on bone health.

Stem cell-based bioregenerative therapy of osteoporosis: literature review

Aging is an inevitable process of our civilization. Since ancient times, scientists have tried to solve the mystery of aging. The research continues to this day. The most common diseases of old age are disorders of the musculoskeletal system. Among them, osteoporosis continues to occupy the third place in the structure of overall morbidity and mortality. Such statistical data make us think about the search for a possible cause of the disease at the molecular level. The purpose of this study was to analyze the literature data on modern directions of osteoporosis treatment, including stem-cells based bioregenerative medicine. An analytical review of literature data was conducted using the information analysis of Medline (PubMed), Web of Science and Scopus databases, Google Scholar and the Cochrane Central Register of Controlled Trials (CENTRAL) from 2018 to 2022 using the keywords “osteoporosis”, bioregenerative therapy”, “stem cell therapy”. Recent results of preclinical experimental studies have shown the effectiveness of the introduction of new bioregenerative technologies. In particular, the use of mesenchymal stem cells, exosomes and miRNAs. Preclinical studies on MSC transplantation in the treatment of osteoporosis indicate an increase in osteogenic differentiation, an increase in BMD. Exosomes also may play multiple roles in the treatment of osteoporosis: improving the disbalance between osteoclasts and osteoblasts, structural modification of exosomes and transmitters’ drug function. The promotion of bone regeneration of exosomes has been shown in animal models. Exosomes with active ingredients can treat a variety of skeletal disorders including osteoporosis and osteoporotic fractures. The results of recent research of the bone disorder treatment based on stem cells therapy have shown convincing prospects for new approaches.

The role of neridronate in the management of osteoporosis: A meta-analysis.

It is estimated that 1 in 3 women and 1 in 5 men over the age of 50 worldwide will experience an osteoporosis fracture during their lives. Neridronate is a third-generation bisphosphonate with established efficacy in metabolic bone disease. It can be used in the treatment of osteoporosis. We aimed to conduct a meta-analysis of the effect of neridronate on the treatment of osteoporosis. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations were used to guide the present study. We searched PubMed and the Cochrane Central Register of Controlled Trials (CENTRAL) for reports published until August 31, 2021, related to neridronate and osteoporosis. The modification of the bone mineral density (BMD, g/cm2) of the patient is the core indicator for neridronate treatment. Significant increases in the BMD of the lumbar spine (mean difference (MD) = 5.99, 95% confidence interval (95% CI): 3.96-8.02), femoral neck (MD = 4.51, 95% CI: 2.01-7.01) and total hip (MD = 2.55, 95% CI: 2.10-3.00) were found. Greater improvement in the BMD of the lumbar spine and femoral neck could also be detected in patients with postmenopausal osteoporosis than with other causes of osteoporosis. Moreover, significant decreases in serum C-telopeptide of collagen type I (sCTX, standardized mean difference (SMD) = -0.84, 95% CI: -1.32--0.37) and bone alkaline phosphatase (ALP, MD = -5.29, 95% CI: -7.31--3.26) levels were observed. The pool analysis of the selected clinical trials indicates the great benefit of neridronate in improving the condition of patients with osteoporosis of all causes, particularly patients with postmenopausal osteoporosis, which causes an increase in BMD as well as in sCTX and bone ALP levels.