ObjectivesTo describe fracture rates, back pain, and health-related quality of life (HRQoL) in po... more ObjectivesTo describe fracture rates, back pain, and health-related quality of life (HRQoL) in postmenopausal women with osteoporosis and prior bisphosphonate therapy, treated with teriparatide for up to 18 months and followed up for a further 18 months.DesignProspective, multinational, and observational study.MethodsData on prior bisphosphonate use, clinical fractures, back pain visual analog scale (VAS), and HRQoL (EQ-5D) were collected over 36 months. Fracture data were summarized in 6-month intervals and analyzed using logistic regression with repeated measures. Changes from baseline in back pain VAS and EQ-VAS were analyzed using a repeated measures model.ResultsOf the 1581 enrolled patients with follow-up data, 1161 (73.4%) had a history of prior bisphosphonate use (median duration: 36 months). Of them, 169 (14.6%) sustained ≥1 fracture during 36-month follow-up. Adjusted odds of fracture were significantly decreased at each 6-month interval compared with the first 6 months of...
Several genome‐wide scans have been performed to detect loci that regulate BMD, but these have yi... more Several genome‐wide scans have been performed to detect loci that regulate BMD, but these have yielded inconsistent results, with limited replication of linkage peaks in different studies. In an effort to improve statistical power for detection of these loci, we performed a meta‐analysis of genome‐wide scans in which spine or hip BMD were studied. Evidence was gained to suggest that several chromosomal loci regulate BMD in a site‐specific and sex‐specific manner.Introduction: BMD is a heritable trait and an important predictor of osteoporotic fracture risk. Several genome‐wide scans have been performed in an attempt to detect loci that regulate BMD, but there has been limited replication of linkage peaks between studies. In an attempt to resolve these inconsistencies, we conducted a collaborative meta‐analysis of genome‐wide linkage scans in which femoral neck BMD (FN‐BMD) or lumbar spine BMD (LS‐BMD) had been studied.Materials and Methods: Data were accumulated from nine genome‐wid...
ABSTRACT Bone mineral density (BMD) measured by densitometry is the elective parameter for the di... more ABSTRACT Bone mineral density (BMD) measured by densitometry is the elective parameter for the diagnosis of osteopenia and osteoporosis. Biochemical markers have been proposed as sensitive indicators of high bone turnover and for monitoring response to antiresorptive treatment. We conducted a retrospective study to investigate the values of biochemical markers of bone metabolism with a view to early diagnosis of osteoporosis and monitoring of hormone replacement and calcitonin therapy. The subjects were 415 women, mean age 51+/-8 years (43-62 years) in peri- and postmenopause, recruited at the Menopause Center of Obstetrics and Gynecology Department of Siena University and divided in five groups. Bone densitometry was performed in all subjects and blood samples were taken for assayed biochemical markers, that is, [osteocalcin (OC), parathyroid hormone (PTH), type 1 procollagen (PICP), and calcitonin (CT)]. Three groups of women were divided into two subgroups: those with normal and those with low BMD (<1 SD). Basal concentrations of PCP1, OC, PTH, and CT were compared in the various groups. Two groups of postmenopausal women with BMD below the normal were treated with estrogen replacement therapy and unmodified eel calcitonin. We evaluated whether some of these biochemical markers of bone turnover could help identify women with low BMD and whether they could be useful for monitoring the results of antiresorptive therapies. Markers of bone formation (PICP and OC) make it possible to distinguish women with high turnover who are at risk for osteoporosis from women with low turnover in menopause. A good correlation was also found between changes in levels of these markers and changes in BMD during treatments, which suggests that the PICP and OC would be useful for monitoring response to antiresorptive therapy.
Oral bisphosphonates and direct oral anticoagulants are related to upper gastrointestinal ulcers.... more Oral bisphosphonates and direct oral anticoagulants are related to upper gastrointestinal ulcers. The present study investigated whether concomitant use of these drugs increase the risk of upper gastrointestinal ulcers and report no increased risk of upper gastrointestinal ulcers compared to the use of either drug alone, when individuals with previous upper gastrointestinal ulcers are excluded. This study examines whether concomitant use of oral bisphosphonates (oBP) and direct oral anticoagulants (DOAC) increases the risk of peptic ulcers more than any drug alone. A population-based cohort study was performed. We sampled a cohort of oBP and DOAC users from a sample of 2,622,742 individuals, consisting of diabetes patients and age- and gender-matched controls, obtained from the Danish National Patient Register. The exposures were concomitant use of oBP and DOAC and single use of DOAC and single use of oBP. The primary endpoint was the first incident peptic ulcer. Information on exposure and outcome were collected from national registries. The period of observation was from 01.01.2008 until 31.12.2018. Unadjusted and adjusted Cox regressions were performed. 8077 individuals received concomitant treatment with DOAC and oBP; 96,451 individuals used DOAC and no oBP; and 118,675 used oBP and no DOAC. The mean duration of follow-up was 1.9 years for concomitant users, 2.5 years for DOAC users, and 4.5 years for oBP users. A total of 4742 individuals with incident peptic ulcers were collected. We observed an increased risk of incident ulcer in users of DOAC and oBP compared to single DOAC treatment in the adjusted analysis (HR = 1.23, 95% CI: 1.03; 1.48). However, the effects were abolished when excluding individuals with a previous ulcer. We observed an increased risk of incident ulcer in users of DOAC and oBP compared to users of oBP in the adjusted model (HR = 1.34, 95% CI: 1.11; 1.63). Based on our results, concomitant use of oBP and DOAC is associated with a slight increase in the risk of peptic ulcers compared to either drug alone. The prescribing physician should weigh the slight increased risk of ulcer in concomitant users of oBP and DOAC with beneficial reductions in stroke and fractures.
Individuals with low socio-economic status (SES) have a more than 25% higher risk of fragility fr... more Individuals with low socio-economic status (SES) have a more than 25% higher risk of fragility fractures than individuals with high SES. Body mass index and lifestyle appear to mediate the effect of SES on fracture risk. Strategies to prevent fractures should aim to reduce unhealthy behaviours through tackling structural inequalities. This systematic review and meta-analysis aimed to evaluate the impact of socio-economic status (SES) on fragility fracture risk. Medline, Embase, and CINAHL databases were searched from inception to 28 April 2021 for studies reporting an association between SES and fragility fracture risk among individuals aged ≥50 years. Risk ratios (RR) were combined in meta-analyses using random restricted maximum likelihood models, for individual-based (education, income, occupation, cohabitation) and area-based (Index of Multiple Deprivation, area income) SES measures. A total of 61 studies from 26 different countries including more than 19 million individuals wer...
The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF ≤ 1%)... more The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF ≤ 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants, as well as rare, population-specific, coding variants. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel loc...
... 19, No. 5 November 1996:557564 Skeletal Responsiveness to Thyroid Hormone Is Not Altered at M... more ... 19, No. 5 November 1996:557564 Skeletal Responsiveness to Thyroid Hormone Is Not Altered at Menopause BL LANGDAHL,' AG LOFT,' N. MOLLER,2 J ... Meunier, PJ, Bianchi, GGS, Edouard, CM, Bernard, JC, Courpron, P., and Vignon, GE Bony manifestations of thyrotoxicosis. ...
In this nationwide register-based cohort study, we found no difference in the risk of fractures i... more In this nationwide register-based cohort study, we found no difference in the risk of fractures in patients discontinuing versus continuing alendronate (ALN) treatment after 5 years. Information on fracture risk in patients discontinuing ALN in a real-life setting is sparse. We aimed to examine ALN discontinuation patterns, compare fracture rates in patients discontinuing versus continuing ALN after 5 years of treatment, and define determinants of fractures in ALN discontinuers. A nationwide population-based cohort study using Danish health registry data. Our source population was individuals who had redeemed ≥ 2 ALN prescriptions between January 1, 1995, and September 1, 2017. We found that 25% of all ALN initiators used ALN for less than 1 year and 43% continued treatment for at least 5 years. We classified n = 1865 as ALN discontinuers and n = 29,619 as ALN continuers. Using Cox proportional hazards regression analysis and an “as-treated” approach, we observed no increased risk of any fracture (incidence rate ratio (IRR) 1.06, 95% CI 0.92–1.23), vertebral fracture (IRR 0.59, 95% CI 0.33–1.05), hip fracture (IRR 1.04, 95% CI 0.75–1.45), or major osteoporotic fracture (IRR 1.05, 95% CI 0.88–1.25) in the ALN discontinuers compared to continuers during a follow-up time of 1.84 ± 1.56 years (mean ± SD) and 2.51 ± 1.60 years, respectively. ALN re-initiation was a major determinant of follow-up among the discontinuers. Old age (> 80 vs. 50–60 years, unadjusted IRR 2.92, 95% CI 1.18–7.24) was the strongest determinant for fractures following ALN discontinuation. In a real-world setting, less than 50% continued ALN treatment for 5 years. We found no difference in the risk of fractures in patients discontinuing versus continuing ALN after 5 years.
World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO-IOF-ESCEO 2020):... more World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO-IOF-ESCEO 2020): Oral Communications Abstracts # International Osteoporosis Foundation and National Osteoporosis Foundation 2021 OC1 EFFICACY AND SAFETY OF ROMOSOZUMAB AMONG POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS AND MILD-TO-MODERATE CHRONIC KIDNEY DISEASE D. Miller, J. Adachi, B.-H. Albergaria, A. M. Cheung, A. Chines, E. Gielen, B. Langdahl, A. Miyauchi, M. Oates, I. R. Reid, N. Ruiz Santiago, M. Vanderkelen, W. Yang, Z. Yu Colorado Center for Bone Research, Golden, United States, McMaster University, Hamilton, Canada, Federal University of Espirito Santo, Vitória, Brazil, University Health Network, University of Toronto, Toronto, Canada, Amgen, Thousand Oaks, United States, Gerontology and Geriatrics, Department of Public Health and Primary Care, KU Leuven & Center for Metabolic Bone Diseases, UZ Leuven, Leuven, Belgium, Aarhus University Hospital, Aarhus, Denmark, Miyauchi Medical Center, Osaka, Jap...
In patients discontinuing ALN after a median of 7.0 years (range 5.0–20.0 years), BMD decreased, ... more In patients discontinuing ALN after a median of 7.0 years (range 5.0–20.0 years), BMD decreased, and bone turnover markers increased within the premenopausal reference range over 2 years. Increased p-CTX after 3 months was associated with greater bone loss at the hip confirming that maintenance of BMD is dependent on continued suppression of bone turnover. It is unknown how to monitor patients discontinuing alendronate (ALN) after more than 5 years. We investigated if BTM measured before or during treatment discontinuation with ALN predict bone loss after 1 or 2 years. PROSA was a cohort study conducted at Aarhus University Hospital including postmenopausal women and men above 50 years treated with ALN ≥ 5 years who had osteopenia at the hip and BMD T-score at the lumbar spine > − 4. ALN was discontinued and BTMs were measured at baseline, months (M) 1, 3, 6, and 12, and DXA was performed at baseline, M6, and M12. We extended the study and measured BTMs and performed DXA at M24. The primary endpoint was if changes in p-CTX at M3 or M6 predict changes in THBMD after 1 year (Clinicaltrials.gov: NCT03051620). We enrolled 136 participants discontinuing ALN after a median of 7.0 years (range 5.0–20.0 years) in PROSA and 124 participants in PROSA Extension. There was a significant decrease in LSBMD − 0.74% ± 0.27, THBMD − 2.65% ± 0.39, FNBMD − 2.35% ± 0.33, and trabecular bone score − 0.97% ± 0.35 and an increase in p-CTX by 61.1% ± 4.7 (p < 0.05 for all) after 24 months. Increase in p-CTX at M3 was associated with bone loss at the hip sites at M12 and M24. In patients discontinuing ALN, BMD decreased significantly and BTMs increased within the reference range over 2 years. An increase in p-CTX after 3 months was associated with greater bone loss at the hip confirming that maintenance of BMD during treatment discontinuation is dependent on continued suppression of bone turnover.
This post hoc analysis of a randomized, double-blind study of postmenopausal women with osteoporo... more This post hoc analysis of a randomized, double-blind study of postmenopausal women with osteoporosis found that there were early increases in bone turnover markers and decreases in bone mineral density after discontinuation of long-term alendronate. These findings might help guide treatment decisions, including monitoring after alendronate withdrawal. The short-term effects of discontinuing long-term bisphosphonates are poorly characterized. This post hoc analysis investigated 1–12-month changes in bone mineral density (BMD) and bone turnover markers (BTM) after alendronate (ALN) discontinuation. Data were from a randomized, double-blind trial of MK-5442 (calcium-sensing receptor antagonist) following oral bisphosphonates, with placebo and continued ALN controls (ClinicalTrials.gov NCT00996801). Postmenopausal women with osteoporosis had received oral bisphosphonate (≥ 3–4 preceding years; ALN for the 12 months pre-screening), continuing on ALN 70 mg/week (n = 87) or placebo (n = 88). At 12 months, least-squares mean percent changes from baseline BMD (placebo vs. ALN) were lumbar spine (LS): – 0.36 vs. 1.29, total hip: – 1.44 vs. 0.46, and femoral neck (FN): – 1.26 vs. – 0.08 (all P < 0.05). BTM levels increased by 1–3 months, to 12 months, with placebo vs. ALN (P < 0.001). FN BMD decline was greater in the placebo subgroup with higher urinary N-terminal cross-linked telopeptides of type I collagen/creatinine [uNTx/Cr] (P < 0.01), and higher serum N-terminal pro-peptide of type 1 collagen [P1NP] levels (P < 0.05), at baseline. There was a trend toward greater FN BMD loss with higher BTM levels at 3 and/or 6 months. Younger age and higher LS BMD at baseline were associated with greater LS BMD loss at 12 months (P = 0.04 and < 0.01, respectively); higher baseline FN BMD predicted greater FN BMD loss (P = 0.04). Early changes in BTM levels and BMD were observed after discontinuation of long-term ALN. Further characterization of factors associated with patients’ risk of bone loss upon bisphosphonate discontinuation is warranted.
Diabetes mellitus (DM) is associated with increased fracture risk. The aim of this systematic rev... more Diabetes mellitus (DM) is associated with increased fracture risk. The aim of this systematic review was to examine the effects of different classes of glucose-lowering drugs on fracture risk in patients with type 2 DM. The heterogeneity of the included studies did not allow formal statistical analyses. Sixty studies were included in the review. Metformin, dipeptidylpeptidase-IV inhibitors, glucagon-like peptide-1 receptor agonists, and sodium–glucose cotransporter 2-inhibitors do not appear to increase fracture risk. Results for insulin and sulphonylureas were more disparate, although there may be an increased fracture risk related to hypoglycemia and falls with these treatments. Glitazones were consistently associated with increased fracture risk in women, although the evidence was sparser in men. New glucose-lowering drugs are continuously being developed and better understanding of these is leading to changes in prescription patterns. Our findings warrant continued research on the effects of glucose-lowering drugs on fracture risk, elucidating the class-specific effects of these drugs.
ObjectivesTo describe fracture rates, back pain, and health-related quality of life (HRQoL) in po... more ObjectivesTo describe fracture rates, back pain, and health-related quality of life (HRQoL) in postmenopausal women with osteoporosis and prior bisphosphonate therapy, treated with teriparatide for up to 18 months and followed up for a further 18 months.DesignProspective, multinational, and observational study.MethodsData on prior bisphosphonate use, clinical fractures, back pain visual analog scale (VAS), and HRQoL (EQ-5D) were collected over 36 months. Fracture data were summarized in 6-month intervals and analyzed using logistic regression with repeated measures. Changes from baseline in back pain VAS and EQ-VAS were analyzed using a repeated measures model.ResultsOf the 1581 enrolled patients with follow-up data, 1161 (73.4%) had a history of prior bisphosphonate use (median duration: 36 months). Of them, 169 (14.6%) sustained ≥1 fracture during 36-month follow-up. Adjusted odds of fracture were significantly decreased at each 6-month interval compared with the first 6 months of...
Several genome‐wide scans have been performed to detect loci that regulate BMD, but these have yi... more Several genome‐wide scans have been performed to detect loci that regulate BMD, but these have yielded inconsistent results, with limited replication of linkage peaks in different studies. In an effort to improve statistical power for detection of these loci, we performed a meta‐analysis of genome‐wide scans in which spine or hip BMD were studied. Evidence was gained to suggest that several chromosomal loci regulate BMD in a site‐specific and sex‐specific manner.Introduction: BMD is a heritable trait and an important predictor of osteoporotic fracture risk. Several genome‐wide scans have been performed in an attempt to detect loci that regulate BMD, but there has been limited replication of linkage peaks between studies. In an attempt to resolve these inconsistencies, we conducted a collaborative meta‐analysis of genome‐wide linkage scans in which femoral neck BMD (FN‐BMD) or lumbar spine BMD (LS‐BMD) had been studied.Materials and Methods: Data were accumulated from nine genome‐wid...
ABSTRACT Bone mineral density (BMD) measured by densitometry is the elective parameter for the di... more ABSTRACT Bone mineral density (BMD) measured by densitometry is the elective parameter for the diagnosis of osteopenia and osteoporosis. Biochemical markers have been proposed as sensitive indicators of high bone turnover and for monitoring response to antiresorptive treatment. We conducted a retrospective study to investigate the values of biochemical markers of bone metabolism with a view to early diagnosis of osteoporosis and monitoring of hormone replacement and calcitonin therapy. The subjects were 415 women, mean age 51+/-8 years (43-62 years) in peri- and postmenopause, recruited at the Menopause Center of Obstetrics and Gynecology Department of Siena University and divided in five groups. Bone densitometry was performed in all subjects and blood samples were taken for assayed biochemical markers, that is, [osteocalcin (OC), parathyroid hormone (PTH), type 1 procollagen (PICP), and calcitonin (CT)]. Three groups of women were divided into two subgroups: those with normal and those with low BMD (&lt;1 SD). Basal concentrations of PCP1, OC, PTH, and CT were compared in the various groups. Two groups of postmenopausal women with BMD below the normal were treated with estrogen replacement therapy and unmodified eel calcitonin. We evaluated whether some of these biochemical markers of bone turnover could help identify women with low BMD and whether they could be useful for monitoring the results of antiresorptive therapies. Markers of bone formation (PICP and OC) make it possible to distinguish women with high turnover who are at risk for osteoporosis from women with low turnover in menopause. A good correlation was also found between changes in levels of these markers and changes in BMD during treatments, which suggests that the PICP and OC would be useful for monitoring response to antiresorptive therapy.
Oral bisphosphonates and direct oral anticoagulants are related to upper gastrointestinal ulcers.... more Oral bisphosphonates and direct oral anticoagulants are related to upper gastrointestinal ulcers. The present study investigated whether concomitant use of these drugs increase the risk of upper gastrointestinal ulcers and report no increased risk of upper gastrointestinal ulcers compared to the use of either drug alone, when individuals with previous upper gastrointestinal ulcers are excluded. This study examines whether concomitant use of oral bisphosphonates (oBP) and direct oral anticoagulants (DOAC) increases the risk of peptic ulcers more than any drug alone. A population-based cohort study was performed. We sampled a cohort of oBP and DOAC users from a sample of 2,622,742 individuals, consisting of diabetes patients and age- and gender-matched controls, obtained from the Danish National Patient Register. The exposures were concomitant use of oBP and DOAC and single use of DOAC and single use of oBP. The primary endpoint was the first incident peptic ulcer. Information on exposure and outcome were collected from national registries. The period of observation was from 01.01.2008 until 31.12.2018. Unadjusted and adjusted Cox regressions were performed. 8077 individuals received concomitant treatment with DOAC and oBP; 96,451 individuals used DOAC and no oBP; and 118,675 used oBP and no DOAC. The mean duration of follow-up was 1.9 years for concomitant users, 2.5 years for DOAC users, and 4.5 years for oBP users. A total of 4742 individuals with incident peptic ulcers were collected. We observed an increased risk of incident ulcer in users of DOAC and oBP compared to single DOAC treatment in the adjusted analysis (HR = 1.23, 95% CI: 1.03; 1.48). However, the effects were abolished when excluding individuals with a previous ulcer. We observed an increased risk of incident ulcer in users of DOAC and oBP compared to users of oBP in the adjusted model (HR = 1.34, 95% CI: 1.11; 1.63). Based on our results, concomitant use of oBP and DOAC is associated with a slight increase in the risk of peptic ulcers compared to either drug alone. The prescribing physician should weigh the slight increased risk of ulcer in concomitant users of oBP and DOAC with beneficial reductions in stroke and fractures.
Individuals with low socio-economic status (SES) have a more than 25% higher risk of fragility fr... more Individuals with low socio-economic status (SES) have a more than 25% higher risk of fragility fractures than individuals with high SES. Body mass index and lifestyle appear to mediate the effect of SES on fracture risk. Strategies to prevent fractures should aim to reduce unhealthy behaviours through tackling structural inequalities. This systematic review and meta-analysis aimed to evaluate the impact of socio-economic status (SES) on fragility fracture risk. Medline, Embase, and CINAHL databases were searched from inception to 28 April 2021 for studies reporting an association between SES and fragility fracture risk among individuals aged ≥50 years. Risk ratios (RR) were combined in meta-analyses using random restricted maximum likelihood models, for individual-based (education, income, occupation, cohabitation) and area-based (Index of Multiple Deprivation, area income) SES measures. A total of 61 studies from 26 different countries including more than 19 million individuals wer...
The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF ≤ 1%)... more The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF ≤ 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants, as well as rare, population-specific, coding variants. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel loc...
... 19, No. 5 November 1996:557564 Skeletal Responsiveness to Thyroid Hormone Is Not Altered at M... more ... 19, No. 5 November 1996:557564 Skeletal Responsiveness to Thyroid Hormone Is Not Altered at Menopause BL LANGDAHL,' AG LOFT,' N. MOLLER,2 J ... Meunier, PJ, Bianchi, GGS, Edouard, CM, Bernard, JC, Courpron, P., and Vignon, GE Bony manifestations of thyrotoxicosis. ...
In this nationwide register-based cohort study, we found no difference in the risk of fractures i... more In this nationwide register-based cohort study, we found no difference in the risk of fractures in patients discontinuing versus continuing alendronate (ALN) treatment after 5 years. Information on fracture risk in patients discontinuing ALN in a real-life setting is sparse. We aimed to examine ALN discontinuation patterns, compare fracture rates in patients discontinuing versus continuing ALN after 5 years of treatment, and define determinants of fractures in ALN discontinuers. A nationwide population-based cohort study using Danish health registry data. Our source population was individuals who had redeemed ≥ 2 ALN prescriptions between January 1, 1995, and September 1, 2017. We found that 25% of all ALN initiators used ALN for less than 1 year and 43% continued treatment for at least 5 years. We classified n = 1865 as ALN discontinuers and n = 29,619 as ALN continuers. Using Cox proportional hazards regression analysis and an “as-treated” approach, we observed no increased risk of any fracture (incidence rate ratio (IRR) 1.06, 95% CI 0.92–1.23), vertebral fracture (IRR 0.59, 95% CI 0.33–1.05), hip fracture (IRR 1.04, 95% CI 0.75–1.45), or major osteoporotic fracture (IRR 1.05, 95% CI 0.88–1.25) in the ALN discontinuers compared to continuers during a follow-up time of 1.84 ± 1.56 years (mean ± SD) and 2.51 ± 1.60 years, respectively. ALN re-initiation was a major determinant of follow-up among the discontinuers. Old age (> 80 vs. 50–60 years, unadjusted IRR 2.92, 95% CI 1.18–7.24) was the strongest determinant for fractures following ALN discontinuation. In a real-world setting, less than 50% continued ALN treatment for 5 years. We found no difference in the risk of fractures in patients discontinuing versus continuing ALN after 5 years.
World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO-IOF-ESCEO 2020):... more World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO-IOF-ESCEO 2020): Oral Communications Abstracts # International Osteoporosis Foundation and National Osteoporosis Foundation 2021 OC1 EFFICACY AND SAFETY OF ROMOSOZUMAB AMONG POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS AND MILD-TO-MODERATE CHRONIC KIDNEY DISEASE D. Miller, J. Adachi, B.-H. Albergaria, A. M. Cheung, A. Chines, E. Gielen, B. Langdahl, A. Miyauchi, M. Oates, I. R. Reid, N. Ruiz Santiago, M. Vanderkelen, W. Yang, Z. Yu Colorado Center for Bone Research, Golden, United States, McMaster University, Hamilton, Canada, Federal University of Espirito Santo, Vitória, Brazil, University Health Network, University of Toronto, Toronto, Canada, Amgen, Thousand Oaks, United States, Gerontology and Geriatrics, Department of Public Health and Primary Care, KU Leuven & Center for Metabolic Bone Diseases, UZ Leuven, Leuven, Belgium, Aarhus University Hospital, Aarhus, Denmark, Miyauchi Medical Center, Osaka, Jap...
In patients discontinuing ALN after a median of 7.0 years (range 5.0–20.0 years), BMD decreased, ... more In patients discontinuing ALN after a median of 7.0 years (range 5.0–20.0 years), BMD decreased, and bone turnover markers increased within the premenopausal reference range over 2 years. Increased p-CTX after 3 months was associated with greater bone loss at the hip confirming that maintenance of BMD is dependent on continued suppression of bone turnover. It is unknown how to monitor patients discontinuing alendronate (ALN) after more than 5 years. We investigated if BTM measured before or during treatment discontinuation with ALN predict bone loss after 1 or 2 years. PROSA was a cohort study conducted at Aarhus University Hospital including postmenopausal women and men above 50 years treated with ALN ≥ 5 years who had osteopenia at the hip and BMD T-score at the lumbar spine > − 4. ALN was discontinued and BTMs were measured at baseline, months (M) 1, 3, 6, and 12, and DXA was performed at baseline, M6, and M12. We extended the study and measured BTMs and performed DXA at M24. The primary endpoint was if changes in p-CTX at M3 or M6 predict changes in THBMD after 1 year (Clinicaltrials.gov: NCT03051620). We enrolled 136 participants discontinuing ALN after a median of 7.0 years (range 5.0–20.0 years) in PROSA and 124 participants in PROSA Extension. There was a significant decrease in LSBMD − 0.74% ± 0.27, THBMD − 2.65% ± 0.39, FNBMD − 2.35% ± 0.33, and trabecular bone score − 0.97% ± 0.35 and an increase in p-CTX by 61.1% ± 4.7 (p < 0.05 for all) after 24 months. Increase in p-CTX at M3 was associated with bone loss at the hip sites at M12 and M24. In patients discontinuing ALN, BMD decreased significantly and BTMs increased within the reference range over 2 years. An increase in p-CTX after 3 months was associated with greater bone loss at the hip confirming that maintenance of BMD during treatment discontinuation is dependent on continued suppression of bone turnover.
This post hoc analysis of a randomized, double-blind study of postmenopausal women with osteoporo... more This post hoc analysis of a randomized, double-blind study of postmenopausal women with osteoporosis found that there were early increases in bone turnover markers and decreases in bone mineral density after discontinuation of long-term alendronate. These findings might help guide treatment decisions, including monitoring after alendronate withdrawal. The short-term effects of discontinuing long-term bisphosphonates are poorly characterized. This post hoc analysis investigated 1–12-month changes in bone mineral density (BMD) and bone turnover markers (BTM) after alendronate (ALN) discontinuation. Data were from a randomized, double-blind trial of MK-5442 (calcium-sensing receptor antagonist) following oral bisphosphonates, with placebo and continued ALN controls (ClinicalTrials.gov NCT00996801). Postmenopausal women with osteoporosis had received oral bisphosphonate (≥ 3–4 preceding years; ALN for the 12 months pre-screening), continuing on ALN 70 mg/week (n = 87) or placebo (n = 88). At 12 months, least-squares mean percent changes from baseline BMD (placebo vs. ALN) were lumbar spine (LS): – 0.36 vs. 1.29, total hip: – 1.44 vs. 0.46, and femoral neck (FN): – 1.26 vs. – 0.08 (all P < 0.05). BTM levels increased by 1–3 months, to 12 months, with placebo vs. ALN (P < 0.001). FN BMD decline was greater in the placebo subgroup with higher urinary N-terminal cross-linked telopeptides of type I collagen/creatinine [uNTx/Cr] (P < 0.01), and higher serum N-terminal pro-peptide of type 1 collagen [P1NP] levels (P < 0.05), at baseline. There was a trend toward greater FN BMD loss with higher BTM levels at 3 and/or 6 months. Younger age and higher LS BMD at baseline were associated with greater LS BMD loss at 12 months (P = 0.04 and < 0.01, respectively); higher baseline FN BMD predicted greater FN BMD loss (P = 0.04). Early changes in BTM levels and BMD were observed after discontinuation of long-term ALN. Further characterization of factors associated with patients’ risk of bone loss upon bisphosphonate discontinuation is warranted.
Diabetes mellitus (DM) is associated with increased fracture risk. The aim of this systematic rev... more Diabetes mellitus (DM) is associated with increased fracture risk. The aim of this systematic review was to examine the effects of different classes of glucose-lowering drugs on fracture risk in patients with type 2 DM. The heterogeneity of the included studies did not allow formal statistical analyses. Sixty studies were included in the review. Metformin, dipeptidylpeptidase-IV inhibitors, glucagon-like peptide-1 receptor agonists, and sodium–glucose cotransporter 2-inhibitors do not appear to increase fracture risk. Results for insulin and sulphonylureas were more disparate, although there may be an increased fracture risk related to hypoglycemia and falls with these treatments. Glitazones were consistently associated with increased fracture risk in women, although the evidence was sparser in men. New glucose-lowering drugs are continuously being developed and better understanding of these is leading to changes in prescription patterns. Our findings warrant continued research on the effects of glucose-lowering drugs on fracture risk, elucidating the class-specific effects of these drugs.
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Papers by B. Langdahl