JBMR Plus最新文献

{"title":"Increased Risk of Fragility Fractures in Patients with Primary Biliary Cholangitis","authors":"Jihye Lim, Ye-Jee Kim, Sehee Kim, Jonggi Choi","doi":"10.1093/jbmrpl/ziae056","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae056","url":null,"abstract":"\u0000 Large-scale studies on the risk of fragility fractures in patients with primary biliary cholangitis (PBC) are limited due to low incidence. We aimed to investigate whether PBC is associated with fragility fractures using real-world nationwide data. The Korean National Health Insurance Service claims data from 2007 to 2020 were analyzed in this population-based cohort study. Patients with PBC (n = 4951) were matched with controls (n = 19 793) using a 1:4 ratio based on age, sex, and follow-up duration. The primary outcome was fragility fracture, which comprised fractures of the vertebra, hip, distal radius, and proximal humerus. The incidence rates (IRs) and hazard ratios (HRs) were determined to assess the impact of PBC on fragility fractures. During the median follow-up period of 5.37 years, 524 patients in the PBC group had fragility fractures (IR, 18.59/1000 person-years [PYs]). After adjusting for covariates, PBC increased the risk of fragility fractures by 1.63-fold (95% confidence interval, 1.20–2.22; P = 0.002). The vertebra and hip were particularly susceptible to fracture in patients with PBC, with adjusted HRs of 1.77 and 2.23, respectively. In the subgroup analysis, the risk of fragility fracture was 2.53-fold higher in men and 1.59-fold higher in women with PBC than that in the respective matched control groups. Considering the morbidity and mortality related to fragility fractures, increasing awareness of fragility fracture risk and implementing appropriate preventive measures in patients with PBC are imperative.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140683474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osteoporosis treatments for intervertebral disc degeneration and back pain: a perspective","authors":"Neharika Bhadouria, N. Holguin","doi":"10.1093/jbmrpl/ziae048","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae048","url":null,"abstract":"\u0000 Low back pain derived from intervertebral disc (IVD) degeneration is a debilitating spinal condition that, despite its prevalence, does not have any intermediary guidelines for treatment between palliative care and invasive surgery. The development of treatments for the IVD is complicated by the variety of resident cell types needed to maintain the regionally distinct structural properties of the IVD that permit the safe, complex motions of the spine. Osteoporosis of the spine increases the risk of vertebral bone fracture and can increase the incidence of back pain. Fortunately, there are a variety of pharmacological treatments for osteoporosis that target osteoblasts, osteoclasts and/or osteocytes to build bone and prevent vertebral fracture. Of particular note, clinical and preclinical studies suggest that commonly prescribed osteoporosis drugs like bisphosphonates, intermittent parathyroid hormone, anti-sclerostin antibody, selective estrogen receptor modulators (SERM) and anti-RANKL inhibitor denosumab may also relieve back pain. Here, we cite clinical and preclinical studies and include unpublished data to support the argument that a subset of these therapeutics for osteoporosis may alleviate low back pain by also targeting the IVD.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140687098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex dimorphic response to osteocyte miR21 deletion in murine calvaria bone as determined by RNAseq analysis","authors":"Gang Peng, Padmini J. Deosthale, Roquelina Pianeta, Hannah M Messermith, Lilian I Plotkin","doi":"10.1093/jbmrpl/ziae054","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae054","url":null,"abstract":"\u0000 Low levels of the microRNA (miR) 21 may explain the increase in osteocyte apoptosis with Cx43-deficient and aged female mice. However, miR21 exerts a sex-divergent role in osteocytes, regulating bone mass and architecture through non-cell autonomous effects on osteoblasts and osteoclasts, via sex-specific regulation of osteocyte cytokine production. miR21 deficiency improves bone strength in females, and, to a higher extent, in male miR21-deficient mice. To understand the molecular basis for the effects of miR21 deletion, mRNA was isolated from miR21fl/fl (controls) or miR21-deficient (by deletion in cells expressing Cre recombinase under the control of the 8 kb fragment of the DMP1 promoter (miR21ΔOt mice). miR21 was 50% lower in miR21ΔOt whole calvaria bone, compared to control mice of the corresponding sex. RNAseq was performed in 4 samples/sex and genotype. There were 152 genes with <0.05 p-value and > 1 absolute log2 fold change in the male data analysis, and expression of most genes was higher in the miR21fl/fl group. Two of the genes, Actn3 and Myh4, had a false discovery rate < 0.1. Gene enrichment analysis of significant genes on both KEGG pathways and GO gene sets shows the significant genes were enriched in muscle contraction. Some muscle related genes like Actn3 were included in multiple significant pathways. For females, only 65 genes had p-value <0.05 and > 1 absolute log2 fold change. Yet, no significant KEGG or GO pathways including ≥5 significant genes were seen, and no overlap of significant genes was found between male and female samples. Therefore, deletion of miR21 has a stronger effect on male transcriptome in calvaria, compared to females. Further, no enrichment of any pathway was detected in female samples. Thus, either there are no differences between two groups in female or the effect size is small, and a larger sample size is needed to uncover miR21-dependent differences.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140686331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical development of EXT608, an investigational parathyroid hormone derivative with extended half-life for the treatment of hypoparathyroidism","authors":"Daniel B Hall, Caroline H Kostyla, Laura M Hales, T. Soliman","doi":"10.1093/jbmrpl/ziae045","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae045","url":null,"abstract":"\u0000 Hypoparathyroidism, a deficiency of parathyroid hormone (PTH), results in hypocalcemia, hyperphosphatemia, and hypercalciuria. The disease is poorly controlled by calcium and vitamin D supplements or native PTH(1-84) replacement therapy. A version of PTH is being developed using D-VITylation technology, whereby vitamin D is conjugated to a therapeutic peptide, which confers a long plasma half-life by virtue of binding to the abundant vitamin D binding protein (DBP). D-VITylation of PTH caused no reduction in activity at the PTHR1 receptor, and resulted in a plasma elimination half-life of 7-15 h in rats and 24-32 h in cynomolgus monkeys. Analysis of steady-state pharmacokinetics as a function of dose showed flat profiles with smaller peak:trough ratios at low doses, indicative of slower subcutaneous absorption. In thyroparathyroidectomized (TPTx) rats, PTH(1-34)-vitamin D conjugates restored serum calcium and phosphate levels into the normal range over the 24 h dosing period, and increased bone turnover markers and reduced bone mineral density. Urinary calcium was initially elevated, but normalized by the end of treatment on Day 27. In healthy monkeys, a single dose of PTH(1-34)-vitamin D conjugates elevated serum calcium levels above the normal range for a period of 24-48 h while simultaneously reducing urinary calcium. Therefore, the lead compound, EXT608, is a promising candidate as a therapeutic that can truly mimic the endogenous activity of PTH and warrants further study in patients with hypoparathyroidism.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140688243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osteoblastic erythropoietin is not required for bone mass accrual","authors":"Giulia Lanzolla, Christophe Merceron, M. Khan, Elena Sabini, Amato Giaccia, Ernestina Schipani","doi":"10.1093/jbmrpl/ziae052","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae052","url":null,"abstract":"\u0000 Erythropoietin, primarily produced by interstitial fibroblasts in the kidney during adulthood, and its receptor are well-known for their crucial role in regulating erythropoiesis. Recent research has unveiled an additional function of circulating erythropoietin in the control of bone mass accrual and homeostasis through its receptor, which is expressed in both osteoblasts and osteoclasts. Notably, cells of the osteoblast lineage can produce and secrete functional erythropoietin upon activation of the hypoxia signaling pathway. However, the physiological relevance of osteoblastic erythropoietin remains to be fully elucidated.\u0000 This study aimed to investigate the potential role of osteoblastic erythropoietin in regulating bone mass accrual and erythropoiesis in young adult mice. To accomplish this, we employed a mutant mouse model lacking erythropoietin specifically in mesenchymal progenitors and their descendants. Our findings indicate that in vivo loss of erythropoietin in the osteoblast lineage does not significantly affect either bone mass accrual or erythropoiesis in young adult mice. Further investigations are necessary to comprehensively understand the potential contribution of erythropoietin produced and secreted by osteoblast cells during aging, repair and under pathological conditions.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140702751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An emergency department-based system intervention to improve osteoporosis screening for older adults at high-risk of fracture","authors":"Lesley E Jackson, Rachel M Skains, A. Mudano, N. Techarukpong, James S Booth, Kenneth G. Saag, Liana Fraenkel, M. Danila","doi":"10.1093/jbmrpl/ziae038","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae038","url":null,"abstract":"\u0000 Falls and osteoporosis are risk factors for fragility fractures. Bone mineral density (BMD) assessment is associated with better preventative osteoporosis care, but it is underutilized by those at high fracture risk. We created a novel electronic medical record (EMR) alert-driven protocol to screen patients in the emergency department (ED) for fracture risk and tested its feasibility and effectiveness in generating and completing referrals for outpatient BMD testing after discharge.\u0000 The EMR alert was configured in two tertiary-care EDs and triggered by the term “fall” in the chief complaint, age (≥65 years for women, ≥70 years for men), and high fall risk (Morse score ≥ 45). The alert electronically notified ED study staff of potentially eligible patients. Participants received osteoporosis screening education and had BMD testing ordered.\u0000 From November 15, 2020 to December 4, 2021, there were 2608 EMR alerts among 2509 patients. We identified 558 patients at high-risk of fracture who were screened for BMD testing referral. Participants were excluded for: serious illness (N = 141), no documented health insurance to cover BMD testing (N = 97), prior BMD testing/recent osteoporosis care (N = 58), research assistant unavailable to enroll (N = 53), concomitant fracture (N = 43), bedridden status (N = 38), chief complaint of fall documented in error (N = 38), long-term care residence (N = 34), participation refusal (N = 32), or hospitalization (N = 3). Of the 16 participants who had BMD testing ordered, 7 scheduled and 5 completed BMD testing.\u0000 EMR alerts can help identify subpopulations who may benefit from osteoporosis screening, but there are significant barriers to identifying eligible and willing patients for screening in the ED. In our study targeting an innovative venue for osteoporosis care delivery, only about 1% of patients at high-risk of fracture scheduled BMD testing after an ED visit. Adequate resources during and after an ED visit are needed to ensure that older adults participate in preventative osteoporosis care.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140708353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osteoporosis GWAS-implicated <i>DNM3</i> locus contextually regulates osteoblastic and chondrogenic fate of mesenchymal stem/progenitor cells through oscillating miR-199a-5p levels.","authors":"Gurcharan Kaur, James A Pippin, Solomon Chang, Justin Redmond, Alessandra Chesi, Andrew D Wells, Tristan Maerz, Struan F A Grant, Rhima M Coleman, Kurt D Hankenson, Yadav Wagley","doi":"10.1093/jbmrpl/ziae051","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae051","url":null,"abstract":"<p><p>Genome wide association study (GWAS)-implicated bone mineral density (BMD) signals have been shown to localize in cis-regulatory regions of distal effector genes using 3D genomic methods. Detailed characterization of such genes can reveal novel causal genes for BMD determination. Here, we elected to characterize the \"<i>DNM3\"</i> locus on chr1q24, where the long non-coding RNA <i>DNM3OS</i> and the embedded microRNA <i>MIR199A2</i> (miR-199a-5p) are implicated as effector genes contacted by the region harboring variation in linkage disequilibrium with BMD-associated sentinel single nucleotide polymorphism, rs12041600. During osteoblast differentiation of human mesenchymal stem/progenitor cells (hMSC), miR-199a-5p expression was temporally decreased and correlated with the induction of osteoblastic transcription factors RUNX2 and Osterix. Functional relevance of miR-199a-5p downregulation in osteoblastogenesis was investigated by introducing miR-199a-5p mimic into hMSC. Cells overexpressing miR-199a-5p depicted a cobblestone-like morphological change and failed to produce BMP2-dependent extracellular matrix mineralization. Mechanistically, a miR-199a-5p mimic modified hMSC propagated normal SMAD1/5/9 signaling and expressed osteoblastic transcription factors RUNX2 and Osterix but depicted pronounced upregulation of SOX9 and enhanced expression of essential chondrogenic genes <i>ACAN, COMP,</i> and <i>COL10A1</i>. Mineralization defects, morphological changes, and enhanced chondrogenic gene expression associated with miR-199a-5p mimic over-expression were restored with miR-199a-5p inhibitor suggesting specificity of miR-199a-5p in chondrogenic fate specification. The expression of both the <i>DNM3OS</i> and miR-199a-5p temporally increased and correlated with hMSC chondrogenic differentiation. Although miR-199a-5p overexpression failed to further enhance chondrogenesis, blocking miR-199a-5p activity significantly reduced chondrogenic pellet size, extracellular matrix deposition, and chondrogenic gene expression. Taken together, our results indicate that oscillating miR-199a-5p levels dictate hMSC osteoblast or chondrocyte terminal fate. Our study highlights a functional role of miR-199a-5p as a BMD effector gene at the <i>DNM3</i> BMD GWAS locus, where patients with cis-regulatory genetic variation which increases miR-199a-5p expression could lead to reduced osteoblast activity.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11056323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140852795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss-of-function OGFRL1 variants identified in autosomal recessive cherubism families","authors":"M. Kittaka, N. Mizuno, H. Morino, Tetsuya Yoshimoto, Tianli Zhu, Sheng Liu, Ziyi Wang, Kotoe Mayahara, Kyohei Iio, Kaori Kondo, Toshio Kondo, Tatsuhide Hayashi, Sarah Coghlan, Yayoi Teno, Andrew Anh Phuong Doan, Marcus Levitan, Roy B Choi, Shinji Matsuda, K. Ouhara, Jun Wan, Annelise M Cassidy, Stephane Pelletier, S. Nampoothiri, Andoni J Urtizbera, Alexander G Robling, M. Ono, Hideshi Kawakami, E. Reichenberger, Yasuyoshi Ueki","doi":"10.1093/jbmrpl/ziae050","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae050","url":null,"abstract":"\u0000 Cherubism (OMIM 118400) is a rare craniofacial disorder in children characterized by destructive jawbone expansion due to the growth of inflammatory fibrous lesions. Our previous studies have shown that gain-of-function mutations in SH3 domain-binding protein 2 (SH3BP2) are responsible for cherubism and that a knock-in mouse model for cherubism recapitulates the features of cherubism, such as increased osteoclast formation and jawbone destruction. To date, SH3BP2 is the only gene identified to be responsible for cherubism. Since not all patients clinically diagnosed with cherubism had mutations in SH3BP2, we hypothesized that there may be novel cherubism genes and that these genes may play a role in jawbone homeostasis. Here, using whole exome sequencing, we identified homozygous loss-of-function variants in the opioid growth factor receptor like 1 (OGFRL1) gene in two independent autosomal recessive cherubism families from Syria and India. The newly identified pathogenic homozygous variants were not reported in any variant databases, suggesting that OGFRL1 is a novel gene responsible for cherubism. Single cell analysis of mouse jawbone tissue revealed that Ogfrl1 is highly expressed in myeloid lineage cells. We generated OGFRL1 knockout mice and mice carrying the Syrian frameshift mutation to understand the in vivo role of OGFRL1. However, neither mouse model recapitulated human cherubism or the phenotypes exhibited by SH3BP2 cherubism mice under physiological and periodontitis conditions. Unlike bone marrow-derived M-CSF-dependent macrophages (BMMs) carrying the SH3BP2 cherubism mutation, BMMs lacking OGFRL1 or carrying the Syrian mutation showed no difference in TNF-ɑ mRNA induction by LPS or TNF-ɑ compared to wild-type BMMs. Osteoclast formation induced by receptor activator of NF-κB ligand (RANKL) was also comparable. These results suggest that the loss-of-function effects of OGFRL1 in humans differ from those in mice and highlight the fact that mice are not always an ideal model for studying rare craniofacial bone disorders.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140725574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cortical and trabecular mechanical properties in the femoral neck vary differently with changes in bone mineral density","authors":"Martin Bittner-Frank, A. Reisinger, O. Andriotis, D. Pahr, P. Thurner","doi":"10.1093/jbmrpl/ziae049","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae049","url":null,"abstract":"\u0000 Osteoporosis is an increasing burden for our ageing society. Fracture risk assessment tool (FRAX) and areal bone mineral density (aBMD) have been mainly used as a surrogate, but only identify 46% of patients sustaining a hip fracture. Adding information about material and mechanical properties might improve the fracture risk prediction. In the current study these properties were assessed of cortical and trabecular bone samples from the human femoral neck. In total, 178 trabeculae were obtained from 10 patients suffering a low-trauma fracture and 10 healthy donors (from a previous study) and 141 cortical specimens were newly manufactured from 17 low-trauma fracture patients and 15 controls. Cyclic tensile tests were performed to extract elastic, plastic, viscous, damage, and failure properties with a rheological model. No significant difference of any investigated property was determined. Interestingly, donor aBMD indicated a significant correlation with the post-yield behavior and damage accumulation (modulus degradation) of cortical bone. Cortical bone indicated a significantly larger apparent modulus (17.2 GPa), yield stress (50 MPa), viscosity (17.9 GPas), and damage accumulation (73%), but a decreased toughness (1.6 MJ/m3), than trabecular bone (8.8 GPa, 30 MPa, 9.3 GPas, 60%, 3.2 MJ/m3, respectively). Qualitatively, cortical bone displayed a linear-elastic phase, followed by a plastic phase with little post-yield hardening. In contrast, trabeculae yielded early, with a pronounced post-yield hardening phase and fractured at larger strains. Only a few correlations between donor mineral status and tissue mechanical behavior were found. It is suggested that the trabecularization of cortical bone with age and disease may not only have structural consequences. Our data indicates that this process may also alter the tissue material properties, i.e. transitioning from stiff elastic cortical to soft, viscous trabecular. This aspect warrants further investigation to determine its role in age- and osteoporosis-related bone fragility.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140723207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"On-time denosumab dosing recovered rapidly during the COVID-19 pandemic, yet remains suboptimal","authors":"Anna M Rzepka, Angela M Cheung, Sandra Kim, Tara Gomes, Suzanne M Cadarette","doi":"10.1093/jbmrpl/ziae027","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae027","url":null,"abstract":"Abstract Timely administration of denosumab every 6 mo is critical in osteoporosis treatment to avoid multiple vertebral fracture risk upon denosumab discontinuation or delay. This study aimed to estimate the immediate and prolonged impact of the COVID-19 pandemic on the timing of denosumab doses. We identified older adults (≥66 yr) residing in the community who were due to receive denosumab between January 2016 and December 2020 using Ontario Drug Benefit data. We completed an interrupted time-series analysis to estimate the impact of the COVID-19 pandemic (March 2020) on the monthly proportion of on-time denosumab doses (183 +/−30 d). Analyses were stratified by user type: patients due for their second dose (novice users), third or fourth dose (intermediate users), or ≥5th dose (established users). In additional analyses, we considered patients living in nursing homes, switching to other osteoporosis drugs, and reported trends until February 2022. We studied 148 554 patients (90.9% female, mean [SD] age 79.6 [8.0] yr) receiving 648 221 denosumab doses. The average pre-pandemic proportion of on-time therapy was steady in the community, yet differed by user type: 64.9% novice users, 72.3% intermediate users, and 78.0% established users. We identified an immediate overall decline in the proportion of on-time doses across all user types at the start of the pandemic: −17.8% (95% CI, −19.6, −16.0). In nursing homes, the pre-pandemic proportion of on-time therapy was similar across user types (average 83.5%), with a small decline at the start of the pandemic: −3.2% (95% CI, −5.0, −1.2). On-time therapy returned to pre-pandemic levels by October 2020 and was not impacted by therapy switching. Although on-time dosing remains stable as of February 2022, approximately one-fourth of patients in the community do not receive denosumab on-time. In conclusion, although pandemic disruptions to denosumab dosing were temporary, levels of on-time therapy remain suboptimal.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140726788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}