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A Comparison of US and Canadian Osteoporosis Screening and Treatment Strategies in Postmenopausal Women.

ABSTRACT: The optimal approach to osteoporosis screening and treatment in postmenopausal women is unclear. We compared (i) the United States Preventive Services Task Force (USPSTF) and Osteoporosis Canada osteoporosis screening strategies; and (ii) the National Osteoporosis Foundation (NOF) and Canadian treatment strategies. We used data from the prospective Women's Health Initiative Observational Study and Clinical Trials of women aged 50 to 79 years at baseline (n?=?117,707 followed for self-reported fractures; n?=?8134 in bone mineral density [BMD] subset). We determined the yield of the screening and treatment strategies in identifying women who experienced major osteoporotic fractures (MOFs) during a 10-year follow-up. Among women aged 50 to 64 years, 23.1% of women were identified for BMD testing under the USPSTF strategy and 52.3% under the Canadian strategy. For women ?65 years, 100% were identified for testing under the USPSTF and Canadian strategies, 35% to 74% were identified for treatment under NOF, and 16% to 37% were identified for treatment under CAROC (range among 5-year age subgroups). Among women who experienced MOF during follow-up, the USPSTF strategy identified 6.7% of women 50 to 54 years-old and 49.5% of women 60 to 64 years-old for BMD testing (versus 54.4% and 60.6% for the Canadian strategy, respectively). However, the specificity of the USPSTF strategy was higher than that of the Canadian strategy among women 50 to 64 years-old. Among women who experienced MOF during follow-up, sensitivity for identifying women as treatment candidates was lowest for both strategies in women aged 50 to 64 (NOF 10% to 38%; CAROC 1% to 15%) and maximal in 75-year-old to 79-year-old women (NOF 82.8%; 51.6% CAROC); specificity declined with advancing age and was lower with the NOF compared to the CAROC strategy. Among women aged 50 to 64 years, the screening and treatment strategies examined had low sensitivity for identifying those who subsequently experience MOF; sensitivity was higher among women ?65 years than among younger women. New screening and treatment algorithms are needed. © 2018 American Society for Bone and Mineral Research.

SUBMITTER: Crandall CJ

PROVIDER: S-EPMC7354844 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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A Comparison of US and Canadian Osteoporosis Screening and Treatment Strategies in Postmenopausal Women.

Crandall Carolyn J CJ Larson Joseph J Manson JoAnn E JE Cauley Jane A JA LaCroix Andrea Z AZ Wactawski-Wende Jean J Datta Mridul M Sattari Maryam M Schousboe John T JT Leslie William D WD Ensrud Kristine E KE

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 20190115 4

The optimal approach to osteoporosis screening and treatment in postmenopausal women is unclear. We compared (i) the United States Preventive Services Task Force (USPSTF) and Osteoporosis Canada osteoporosis screening strategies; and (ii) the National Osteoporosis Foundation (NOF) and Canadian treatment strategies. We used data from the prospective Women's Health Initiative Observational Study and Clinical Trials of women aged 50 to 79 years at baseline (n = 117,707 followed for self-reported fr ...[more]

PMID: 30536628

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Project description:BackgroundTo evaluate the prevalence and treatment of postmenopausal women with osteoporosis in recent years, analyze differences between the prevalence diagnosed by physicians and the prevalence detected by bone mineral density (BMD), and observe the trends of prevalence and treatment rate of osteoporosis in postmenopausal women over time are of great value for the management of osteoporosis.MethodsThis cross-sectional study collected the data of 4012 postmenopausal women from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2010, 2013 to 2014 and 2017 to 2018. The prevalence of osteoporosis and osteopenia as well as the treatment rate of osteoporosis were analyzed using Mann-Kendall trend test. Subgroup analysis was conducted in different age, race, body mass index (BMI), diabetes, hypertension, or glucocorticoid use groups.ResultsThe overall prevalence of physician diagnosed of osteoporosis was 17.4% and was fluctuated in a small range and remained relatively stable within a certain range (Mann-Kendall trend test: Z = 2.20, P = 0.027) during 2005-2018. The prevalence of osteoporosis in postmenopausal women determined by bone mineral density (BMD) examination reached 9.2% during the five cycles. From 2005 to 2018, the prevalence of physician diagnosed osteoporosis fluctuated in a small range. For osteopenia measured by BMD, the prevalence was 59.6% and a gradual increasing trend was found between 2005 and 2018 (Mann-Kendall trend test: Z = 2.20, P = 0.027). Among patients with physician diagnosed osteoporosis, the treatment rate reached 70.49%. The treatment rate of physician diagnosed osteoporosis was decreased from 2005 to 2008, and further decreased from 2009 to 2018 (Mann-Kendall trend test: Z = -2.20, P = 0.027). The actual treatment rate of osteoporosis patients was 55.53%. During 2005-2018, the actual treatment rate of osteoporosis showed a continuous decline (Mann-Kendall trend test: Z = -2.20, P = 0.027).ConclusionOsteoporosis management might be insufficient and more efforts are needed to improve the diagnosis and treatment rates of osteoporosis in postmenopausal women.

Project description:INTRODUCTION:Long-term treatment is used in patients with osteoporosis, and bisphosphonates (BPs) are the most commonly prescribed medications. However, in some patients this therapy is not effective, cause different side effects and complications. Unfortunately, at least one year is needed to identify and confirm an ineffectiveness of BPs therapy on bone mineral density (BMD). Among other factors, a response to BPs therapy may also be explained by genetic factors. The aim of this study was to analyze the influence of SOST, PTH, FGF2, FDPS, GGPS1, and LRP5 gene variants on the response to treatment with aminobisphosphonates. MATERIALS AND METHODS:Women with postmenopausal osteoporosis were included to this study if they used aminobisphosphonates for at least 12 months. Exclusion criteria were: persistence on BPs therapy less than 80%, bone metabolic diseases, diseases deemed to affect bone metabolism, malignant tumours, using of any medications influencing BMD. The study protocol was approved by the local ethics committee. The BMD at the lumbar spine and femoral neck were measured using dual x-ray absorptiometry (GE Lunar) before and at least 12 months after treatment with BPs. According to BMD change, patients were divided in two groups-responders and non-responders to BPs terapy. Polymorphic variants in SOST, PTH, FGF2, FDPS, GGPS1, and LRP5 genes were determined using PCR analysis with TaqMan probes (Thermo Scientific). RESULTS:In total, 201 women with BPs therapy were included in the study. No statistically significant differences were observed in age, age at menopause, weight, height, BMI and baseline BMD levels between responders (122 subjects) and non-responders (79 subjects). As single markers, the SOST rs1234612 T/T (OR = 2.3; P = 0.02), PTH rs7125774 T/T (OR = 2.8, P = 0.0009), FDPS rs2297480 G/G (OR = 29.3, P = 2.2×10-7), and GGPS1 rs10925503 C/C+C/T (OR = 2.9; P = 0.003) gene variants were over-represented in non-responders group. No significant association between FGF2 rs6854081 and LRP5 rs3736228 gene variants and response to BPs treatment was observed. The carriers of T-T-G-C allelic combination (constructed from rs1234612, rs7125774, rs2297480, and rs10925503) were predisposed to negative response to BPs treatment (OR = 4.9, 95% CI 1.7-14.6, P = 0.005). The C-C-T-C combination was significantly over-represented in responders (OR = 0.1, 95% CI 0.1-0.5, P = 0.006). CONCLUSIONS:Our findings highlight the importance of identified single gene variants and their allelic combinations for pharmacogenetics of BPs therapy of osteoporosis. Complex screening of these genetic markers could be used as a new strategy for personalized antiresorptive therapy.

Project description:ContextIn postmenopausal women, bone mineral density (BMD) declines after teriparatide therapy is stopped. The pattern of BMD loss after teriparatide therapy is stopped in men is less clear.ObjectiveThe aim of the study was to determine whether the pattern of teriparatide-induced bone accrual and post-teriparatide bone loss differs between postmenopausal women and eugonadal men.DesignWe conducted a prospective cohort substudy.PatientsThe study included 14 postmenopausal women and 17 eugonadal men, ages 46-85 yr, with lumbar spine or femoral neck BMD T-scores below -2.InterventionTeriparatide (37 microg sc daily) was administered for 24 months, followed by 12 months off therapy.Main outcome measuresWe measured BMD at various anatomic sites by dual-energy x-ray absorptiometry, trabecular spine BMD by quantitative computed tomography, and bone turnover markers during the treatment and observation periods. The response to teriparatide administration and discontinuation was compared between females and males.ResultsBMD of the spine, femoral neck, total hip, and trabecular spine increased similarly during the treatment period in men and women, whereas BMD at the radius was stable in men but decreased by 8.1 +/- 3.3% in women (P < 0.0001). After teriparatide was stopped, BMD at the posterior-anterior spine decreased by 7.1 +/- 3.8% in women and by 4.1 +/- 3.5% in men (P = 0.036). BMD at the total hip and femoral neck decreased by 3.8 +/- 3.9 and 3.1 +/- 4.3%, respectively, in women but remained stable in men (P < 0.05 for both sites). BMD at the distal radius remained stable in men but increased in women by 1.6 +/- 3.1% (P = 0.069).ConclusionsTeriparatide appears to increase BMD similarly in postmenopausal women and eugonadal men with osteoporosis. After teriparatide is stopped, the decline in BMD is greater in women than in men. If confirmed in larger cohorts, these findings would suggest that the indication for immediate antiresorptive therapy after teriparatide may not be as urgent in men as in women.

Project description:OBJECTIVES:To determine the mechanisms of ubiquitination in postmenopausal osteoporosis and investigate the ubiquitinated spectrum of novel targets between healthy postmenopausal women and postmenopausal osteoporosis patients, we performed ubiquitylome analysis of the whole blood of postmenopausal women and postmenopausal osteoporosis patients. METHODS:To obtain a more comprehensive understanding of the postmenopausal osteoporosis mechanism, we performed a quantitative assessment of the ubiquitylome in whole blood from seven healthy postmenopausal women and seven postmenopausal osteoporosis patients using high-performance liquid chromatography fractionation, affinity enrichment, and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). To examine the ubiquitylome data, we performed enrichment analysis using an ubiquitylated amino acid motif, Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. RESULTS:Altogether, 133 ubiquitinated sites and 102 proteins were quantified. A difference of more than 1.2 times is considered significant upregulation and less than 0.83 significant downregulation; 32 ubiquitinated sites on 25 proteins were upregulated and 101 ubiquitinated sites on 77 proteins were downregulated. These quantified proteins, both with differently ubiquitinated sites, participated in various cellular processes, such as cellular processes, biological regulation processes, response to stimulus processes, single-organism and metabolic processes. Ubiquitin conjugating enzyme activity and ubiquitin-like protein conjugating enzyme activity were the most highly enriched in molecular function of upregulated sites with corresponding proteins, but they were not enriched in downregulated in sites with corresponding proteins. The KEGG pathways analysis of quantified proteins with differentiated ubiquitinated sites found 13 kinds of molecular interactions and functional pathways, such as glyoxylate and decarboxylate metabolism, dopaminergic synapse, ubiquitin-mediated proteolysis, salivary secretion, coagulation and complement cascades, Parkinson's disease, and hippo signaling pathway. In addition, hsa04120 ubiquitin-mediated proteolysis was the most highly enriched in proteins with upregulated sites, hsa04610 complement and coagulation cascades was the most highly enriched in proteins with downregulated ubiquitinated sites, and hsa04114 Oocyte meiosis was the most highly enriched among all differential proteins. CONCLUSION:Our study expands the understanding of the spectrum of novel targets that are differentially ubiquitinated in whole blood from healthy postmenopausal women and postmenopausal osteoporosis patients. The findings will contribute toward our understanding of the underlying proteostasis pathways in postmenopausal osteoporosis and the potential identification of diagnostic biomarkers in whole blood.

Dataset Information

A Comparison of US and Canadian Osteoporosis Screening and Treatment Strategies in Postmenopausal Women.

Publications

A Comparison of US and Canadian Osteoporosis Screening and Treatment Strategies in Postmenopausal Women.

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