-
1.
Mortality risk reduction differs according to bisphosphonate class: a 15-year observational study.
Bliuc, D, Tran, T, van Geel, T, Adachi, JD, Berger, C, van den Bergh, J, Eisman, JA, Geusens, P, Goltzman, D, Hanley, DA, et al
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2019;(4):817-828
Abstract
UNLABELLED In this prospective cohort of 6120 participants aged 50+, nitrogen-bisphosphonates but not non-nitrogen bisphosphonates were associated with a significant 34% mortality risk reduction compared to non-treated propensity score matched controls. These findings open new avenues for research into mechanistic pathways. INTRODUCTION Emerging evidence suggests that bisphosphonates (BP), first-line treatment of osteoporosis, are associated with reduced risks for all-cause mortality. This study aimed to determine the association between different BP types and mortality risk in participants with or without a fracture. METHODS A prospective cohort study of users of different BPs matched to non-users by propensity score (age, gender, co-morbidities, fragility fracture status) and time to starting the BP medication from the population-based Canadian Multicentre Osteoporosis Study from nine Canadian centres followed from 1995 to 2013. Mortality risk for bisphosphonate users vs matched non-users was assessed using pairwise multivariable Cox proportional hazards models. RESULTS There were 2048 women and 308 men on BP and 1970 women and 1794 men who did not receive medication for osteoporosis. The relationship between BP and mortality risk was explored in three separate 1:1 propensity score-matched cohorts of BP users and no treatment (etidronate, n = 599, alendronate, n = 498, and risedronate n = 213). Nitrogen BP (n-BP) (alendronate and risedronate) was associated with lower mortality risks [pairwise HR, 0.66 (95% CI, 0.48-0.91)] while the less potent non-n-BP, etidronate, was not [pairwise HR: 0.89 (95% CI, 0.66-1.20)]. A direct comparison between n-BP and etidronate (n = 340 pairs) also suggested a better survival for n-BP [paired HR, 0.47 (95%CI, (95% CI, 031-0.70)] for n-BP vs. etidronate]. CONCLUSION Compared to no treatment, nitrogen but not non-nitrogen bisphosphonates appear to be associated with better survival.
-
2.
Overwhelming Underuse of Bisphosphonates in French Nursing Home Residents After Proximal Femoral Fracture.
Le Floch, P, Kermarrec, P, Gentric, A
The journal of nutrition, health & aging. 2019;(4):378-380
-
-
Free full text
-
Abstract
OBJECTIVE To evaluate the prescription of bisphosphonates in female nursing home residents aged 75 and older with a history of proximal femoral fracture. DESIGN Observational descriptive study, led in Brest, France, between June and August 2015. SETTING 12 nursing homes in Brest, France. PARTICIPANTS Female nursing home residents, aged 75 and older, with a history of proximal femoral fracture were included. Exclusion criteria were contraindications to bisphosphonate treatment and residents restricted to bed and chair. MEASUREMENTS The primary endpoint was the evaluation of prescription of bisphosphonates at the time of the study. The secondary endpoints were to evaluate vitamin D supplementation and factors associated with bisphosphonate prescription. RESULTS 12 of the 116 included residents (10.3 %) received bisphosphonates. 66.4 % received vitamin D supplementation. CONCLUSION Despite successive French and international recommendations, there is still a very important underuse of treatment by bisphosphonates in old institutionalized female patients with a very high risk of fracture.
-
3.
Prevalence and incidence of osteoporotic fractures in patients on long-term glucocorticoid treatment for rheumatic diseases: the Glucocorticoid Induced OsTeoporosis TOol (GIOTTO) study.
Rossini, M, Viapiana, O, Vitiello, M, Malavolta, N, La Montagna, G, Maddali Bongi, S, Di Munno, O, Nuti, R, Manzini, CU, Ferri, C, et al
Reumatismo. 2017;(1):30-39
Abstract
Osteoporosis and fractures are common and invalidating consequences of chronic glucorticoid (GC) treatment. Reliable information regarding the epidemiology of GC induced osteoporosis (GIOP) comes exclusively from the placebo group of randomized clinical trials while observational studies are generally lacking data on the real prevalence of vertebral fractures, GC dosage and primary diagnosis. The objective of this study was to evaluate the prevalence and incidence of osteoporotic fractures and to identify their major determinants (primary disease, GC dosage, bone mineral density, risk factors, specific treatment for GIOP) in a large cohort of consecutive patients aged >21 years, on chronic treatment with GC (≥5 mg prednisone - PN - equivalent) and attending rheumatology centers located all over Italy. Glucocorticoid Induced OsTeoporosis TOol (GIOTTO) is a national multicenter cross-sectional and longitudinal observational study. 553 patients suffering from Rheumatoid Arthritis (RA), Polymyalgia Rheumatica (PMR) and Connective Tissue Diseases (CTDs) and in chronic treatment with GCs were enrolled. Osteoporotic BMD values (T score <-2.5) were observed in 28%, 38% and 35% of patients with CTDs, PMR or RA at the lumbar spine, and in 18%, 29% and 26% at the femoral neck, respectively. Before GC treatment, prevalent clinical fractures were reported by 12%, 37% and 17% of patients with CTDs, PMR, or RA, respectively. New clinical fragility fractures during GC treatment were reported by 12%, 10% and 23% of CTDs, PMR and RA patients, respectively. Vertebral fractures were the prevailing type of fragility fracture. More than 30% of patients had recurrence of fracture. An average of 80% of patients were in supplementation with calcium and/or vitamin D during treatment with GCs. Respectively, 64%, 80%, and 72% of the CTDs, PMR and RA patients were on pharmacological treatment for GIOP, almost exclusively with bisphosphonates. The GIOTTO study might provide relevant contributions to clinical practice, in particular by highlighting and quantifying in real life the prevalence of GIOP and relative fractures, the frequency of the main risk factors, and the currently sub-optimal prevention. Moreover, these results emphasize the importance of the underlying rheumatic disease on the risk of GIOP associated fractures.
-
4.
Long-term Effects of Neridronate in Adults with Osteogenesis Imperfecta: An Observational Three-Year Italian Study.
Viapiana, O, Idolazzi, L, Fassio, A, Orsolini, G, Rossini, M, Adami, G, Bertoldo, F, Gatti, D
Calcified tissue international. 2017;(4):341-347
Abstract
The aim of this study was to assess the long-term efficacy and safety of i.v. neridronate in the treatment of osteogenesis imperfecta (OI). One hundred and fourteen patients affected by OI were included in the study. Neridronate was administered by i.v. infusion at the dosage of 2 mg/kg, up to a maximum of 100 mg at three-month intervals for 3 years. Dual X-ray absorptiometry of the lumbar spine, hip, and ultradistal and proximal radius were evaluated every 6 months. Blood calcium, phosphate, albumin, fasting urinary calcium/creatinine ratio, total serum alkaline phosphatase, and bone alkaline phosphatase were obtained at baseline and every 3 months. The mean lumbar spine and total hip BMD significantly increased from baseline to any time point (p < 0.001). The mean ultradistal radius BMD significantly increased from baseline only at month 18 (p = 0.026), 30 (p = 0.046), and 36 (p = 0.013), respectively. The mean proximal radius BMD did not change during the whole observation. The levels of bone turnover markers significantly decreased from baseline to any post-baseline observation time. The study was not able to find any statistically significant effect on fracture risk (p = 0.185). The percentage of patients with fractures was unaltered during treatment as compared to the 3-year period before treatment. The most common AEs were fragility fractures, back pain, arthralgia, fever, and joint sprain. An acute phase reaction was reported in 26 (22.8%) patients. None of the reported SAEs were considered as treatment-related. Long-term treatment with i.v. neridronate has positive effects on BMD and bone turnover markers with a good safety profile, although no significant effect on the risk of fracture was observed.
-
5.
Use of Bisphosphonates and Risk of Breast Cancer in a French Cohort of Postmenopausal Women.
Fournier, A, Mesrine, S, Gelot, A, Fagherazzi, G, Baglietto, L, Clavel-Chapelon, F, Boutron-Ruault, MC, Chabbert-Buffet, N
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2017;(28):3230-3239
Abstract
Purpose To assess whether bisphosphonate (BP) use is associated with decreased breast cancer incidence in a cohort of postmenopausal women. Methods The study population included 64,438 postmenopausal women participating in the French E3N (Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale) prospective cohort, with data self-reported in biennial questionnaires matched with data from a drug reimbursement database. Exposure to BPs and the use of other osteoporosis treatments during follow-up were determined using reimbursement data. Other covariates (breast cancer risk factors, clinical risk factors for osteoporotic fractures, and bone mineral density surveillance) originated from the questionnaires. Hazard ratios (HRs) of breast cancer were estimated using Cox proportional hazards models, considering exposure as a time-varying variable. Results Over an average of 7.2 years of follow-up (2004 to 2011), 2,407 first primary breast cancer cases were identified. The HR of breast cancer associated with exposure to BPs was 0.98 (95% CI, 0.85 to 1.12). We found no effect modification by age, body mass index, time since menopause, use of hormone replacement therapy, use of calcium supplements, or use of vitamin D supplements. There was no heterogeneity across BP molecules and no trend according to cumulative dose, duration of use, or time since last use. We observed a decrease in breast cancer risk restricted to the year after treatment initiation (HR, 0.56; 95% CI, 0.36 to 0.87), which was likely explained by healthy screenee bias. Finally, we did not find any variation in HRs across breast carcinomas defined by their estrogen receptor or invasive or in situ status. Conclusion In our observational cohort of postmenopausal women observed from 2004 to 2011, BP use, likely prescribed for the management of osteoporosis, was not associated with decreased breast cancer incidence.
-
6.
Low Bone Density and Bisphosphonate Use and the Risk of Kidney Stones.
Prochaska, M, Taylor, E, Vaidya, A, Curhan, G
Clinical journal of the American Society of Nephrology : CJASN. 2017;(8):1284-1290
-
-
Free full text
-
Abstract
BACKGROUND AND OBJECTIVES Previous studies have demonstrated lower bone density in patients with kidney stones, but no longitudinal studies have evaluated kidney stone risk in individuals with low bone density. Small studies with short follow-up reported reduced 24-hour urine calcium excretion with bisphosphonate use. We examined history of low bone density and bisphosphonate use and the risk of incident kidney stone as well as the association with 24-hour calcium excretion. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We conducted a prospective analysis of 96,092 women in the Nurses' Health Study II. We used Cox proportional hazards models to adjust for age, body mass index, thiazide use, fluid intake, supplemental calcium use, and dietary factors. We also conducted a cross-sectional analysis of 2294 participants using multivariable linear regression to compare 24-hour urinary calcium excretion between participants with and without a history of low bone density, and among 458 participants with low bone density, with and without bisphosphonate use. RESULTS We identified 2564 incident stones during 1,179,860 person-years of follow-up. The multivariable adjusted relative risk for an incident kidney stone for participants with history of low bone density compared with participants without was 1.39 (95% confidence interval [95% CI], 1.20 to 1.62). Among participants with low bone density, the multivariable adjusted relative risk for an incident kidney stone for bisphosphonate users was 0.68 (95% CI, 0.48 to 0.98). In the cross-sectional analysis of 24-hour urine calcium excretion, the multivariable adjusted mean difference in 24-hour calcium was 10 mg/d (95% CI, 1 to 19) higher for participants with history of low bone density. However, among participants with history of low bone density, there was no association between bisphosphonate use and 24-hour calcium with multivariable adjusted mean difference in 24-hour calcium of -2 mg/d (95% CI, -25 to 20). CONCLUSIONS Low bone density is an independent risk factor for incident kidney stone and is associated with higher 24-hour urine calcium excretion. Among participants with low bone density, bisphosphonate use was associated with lower risk of incident kidney stone but was not independently associated with 24-hour urine calcium excretion.
-
7.
Use of oral bisphosphonates in primary prevention of fractures in postmenopausal women: a population-based cohort study.
Real, J, Galindo, G, Galván, L, Lafarga, MA, Rodrigo, MD, Ortega, M
PloS one. 2015;(4):e0118178
Abstract
OBJECTIVE To compare incidence of first osteoporotic fracture in two cohorts of postmenopausal women, one treated with bisphosphonates and the other only with calcium and vitamin D. DESIGN Retrospective population cohort study with paired matching based on data from electronic health records. SETTING Women aged 60 years and older in 2005, from 21 primary care centers in a healthcare region of Spain. PARTICIPANTS Two groups of women aged 60 years and older (n = 1208), prescribed either calcium and vitamin D (CalVitD) or bisphosphonates (BIPHOS) with or without calcium and vitamin D, were compared for the end point of first recorded osteoporotic-related fracture, with 5-years follow-up. MAIN OUTCOME MEASURE Incidence of first fracture: Vertebral fracture, osteoporosis with pathological fracture, fracture of the upper humeral epiphysis, fracture of the lower radial epiphysis, or femur fracture. RESULTS Estimated 10-year risk of fracture was 11.4% (95% confidence interval: 9.6 to 13.2), 11.8% (9.2 to 14.3) in the BIPHOS group and 11.1% (8.6 to 13.6) in the CalVitD group. No significant differences were found between groups in total fractures (Hazard ratio = 0.934 (0.67 to 1.31)) or location (vertebral, femoral, radial or humeral). CONCLUSIONS In postmenopausal women, bisphosphonates have not been shown to better decrease risk of first fracture compared with calcium and vitamin D therapy alone.
-
8.
Comorbidities, bone-sparing agent prescription history and their determinants among postmenopausal women in UK primary care settings: a retrospective database study.
Feudjo-Tepie, M, Ferguson, S, Roddam, A, Taylor, A, Bayly, J, Critchlow, C
Archives of osteoporosis. 2015;:41
Abstract
SUMMARY Distinguishing oral bisphosphonates from other bone-sparing therapies, this retrospective observational study, first, characterized treated osteoporosis patients in the UK, and secondly, explored factors associated with the risk of discontinuation or switching between therapies. The latter should be considered when evaluating real-world data. PURPOSE This retrospective observational study evaluated the characteristics of women with postmenopausal osteoporosis, including comorbidities and determinants of treatment patterns with bone-sparing agents. METHODS The UK Clinical Practice Research Datalink was used to identify postmenopausal women (aged ≥50 years) treated with a bone-sparing agent or diagnosed with osteoporosis between 1 January 1993 and 31 December 2008. Two non-mutually-exclusive subpopulations were defined: (1) patients active in the database on 31 December 2008; (2) patients treated with a bone-sparing agent since 1 January 1993. Subpopulation 1 was used to describe patient comorbidities and osteoporosis treatment history, and subpopulation 2 was used to explore the characteristics associated with bone-sparing treatment patterns use via multivariable regression for repeated multinomial responses. RESULTS A total of 62,657 individuals met the inclusion criteria; subpopulation 1 comprised 38,469 women (61.4%), of whom 21,687 received a bone-sparing agent in 2008 (99.7% oral bisphosphonates and the remainder other agents). Those receiving other agents were more likely to have had previous treatment with bone-sparing agents, to have experienced previous fractures, and to have visited their doctor more frequently. Analyses also identified several comorbidities associated with an increased risk of discontinuation of bone-sparing agents, including heart disease, gastrointestinal disease, and renal failure. Anticonvulsant use was associated with a dramatic increase in the risk of switching. CONCLUSIONS Several patient characteristics were associated with discontinuation of, or switching between, bone-sparing treatments. Patients receiving bone-sparing medication other than oral bisphosphonates were more likely to have comorbid conditions and a history of fracture and to have taken an oral bisphosphonate previously.
-
9.
Factors associated with bisphosphonate treatment failure in postmenopausal women with primary osteoporosis.
Cairoli, E, Eller-Vainicher, C, Ulivieri, FM, Zhukouskaya, VV, Palmieri, S, Morelli, V, Beck-Peccoz, P, Chiodini, I
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2014;(4):1401-10
Abstract
UNLABELLED Among 97 postmenopausal women with primary osteoporosis, adequate calcium and vitamin D supplementation, and good compliance to a 36-month bisphosphonate treatment, the 25.8% of patients are inadequate responders. Current smoking and a bone turnover in the upper part of the normal range increase the risk of treatment failure. INTRODUCTION To evaluate the prevalence of the bisphosphonate treatment failure and its possible associated factors in women with primary osteoporosis (PO). METHODS We studied 97 previously untreated postmenopausal women with PO and fragility fractures and/or a FRAX® 10-year probability of a major osteoporotic fracture ≥ 7.5%, before and after a 36-month treatment with alendronate or risedronate and adequate vitamin D supplementation with good compliance. At baseline and after 36 months, lumbar spine (LS) and femoral bone mineral density (BMD) were assessed by Dual X-ray absorptiometry and vertebral fractures by spinal radiographs. Spinal deformity index (SDI) was calculated. Treatment failure was defined by the presence of ≥ 2 incident fragility fractures and/or a BMD decrease greater than the least significant change. RESULTS Bisphosphonate treatment failure was observed in 25.8% of patients. Age, body mass index, years since menopause, familiar history of hip fracture, number of falls, type of bisphosphonate used, 25-hydroxyvitamin D levels (25OHVitD), BMD, SDI, and FRAX® score at baseline were not different between responders and inadequate responders. Treatment failure was associated with current smoking (OR 3.22, 95% CI 1.10-9.50, P = 0.034) and baseline alkaline phosphatase total activity levels ≥ 66.5 U/L (OR 4.22, 95% CI 1.48-12.01, P = 0.007), regardless of age, number of falls, LS BMD, and baseline SDI. CONCLUSIONS The 25.8 % of PO postmenopausal women inadequately responds to bisphosphonates, despite a good compliance to therapy and normal 25OHVitD levels. The current smoking and bone turnover in the upper part of the normal range are associated with the inadequate response to bisphosphonates.