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Cortical Bone Material Strength Index and Bone Microarchitecture in Postmenopausal Women With Atypical Femoral Fractures.
Popp, KL, Caksa, S, Martinez-Betancourt, A, Yuan, A, Tsai, J, Yu, EW, Bouxsein, ML
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2019;(1):75-82
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Abstract
Atypical femoral fractures are rare fractures that occur in the subtrochanteric or diaphyseal region of the femur with minimal or no trauma. Though the association of atypical femoral fractures (AFFs) and bisphosphonate (BP) use is a growing concern in the management of osteoporosis, currently there is little knowledge about which patients may be at risk for an atypical femoral fracture. Given that these fractures initiate in the femoral cortex, we aimed to determine whether cortical bone tissue properties (bone material strength index; BMSi), as measured by in vivo impact microindentation, are altered in atypical fracture patients. We also aimed to identify factors associated with the BMSi measurements. We enrolled postmenopausal women with recent AFFs (n = 15) or hip fractures (Hip Fxs; n = 20), long-term (>5 years) BP users (n = 30), and treatment naïve controls (n = 88). We measured total hip and femoral neck BMD by DXA, cortical bone microstructure at the distal tibia by HR-pQCT, and BMSi at the midtibia by impact microindentation. BMSi values were similar in all groups, with no effects of long-term BP use or lower values in patients with AFFs or Hip Fxs, even after multivariable adjustment. BMSi measurements were independent of age, femoral BMD, duration of BP treatment, vitamin D level, and cortical bone microstructure, including cortical porosity and cortical tissue mineral density. In conclusion, impact microindentation values are not negatively affected by long-term BP use and do not appear to discriminate individuals who suffer AFFs. Thus, our results do not support clinical use of impact microindentation to identify those at risk for AFFs. This remains to be verified in larger studies. © 2018 American Society for Bone and Mineral Research.
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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.
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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.
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The nature of osteoporotic low back pain without acute vertebral fracture: A prospective multicenter study on the analgesic effect of monthly minodronic acid hydrate.
Fujimoto, K, Inage, K, Orita, S, Yamashita, M, Abe, K, Yamagata, M, Sainoh, T, Akazawa, T, Kinoshita, T, Nemoto, T, et al
Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association. 2017;(4):613-617
Abstract
BACKGROUND Patients with osteoporosis but no evidence of fracture can sometimes report low back pain. However, few studies have evaluated the nature of osteoporotic low back pain in a clinical situation. Therefore, the aim of this study was to examine the nature of osteoporotic low back pain without fracture, and the analgesic effect of minodronic acid hydrate on such pain. METHODS The current study examined 136 patients with osteoporotic low back pain and no lower extremity symptoms. The following factors were evaluated before and after minodronic acid hydrate administration: the nature of osteoporotic low back pain was evaluated using the painDETECT questionnaire, numeric rating scale (NRS) score for low back pain at rest and in motion, bone mineral density (BMD) of the lumbar spine, and the serum concentration of tartrate-resistant acid phosphatase 5b (TRACP-5b) as a bone metabolism marker. RESULTS A total of 113 patients were enrolled. The painDETECT questionnaire revealed the percentage of patients with nociceptive pain and neuropathic or mixed pain was approximately 85% and 15%, respectively. the average NRS scores for low back pain at rest decreased significantly 2 months after treatment (p = 0.01), while those in motion decreased significantly 1 month after treatment (p = 0.04). The average lumbar spine BMD tended to increase after treatment, but not significantly. On the other hand, the changes in the average serum concentration of TRACP-5b did significantly decrease 1 month after treatment. There was a significant positive correlation between the rate of NRS score improvement for low back pain at rest, and the rate of improvement in serum concentration of TRACP-5b (p < 0.05). CONCLUSIONS Osteoporotic low back pain consisted of 85% nociceptive pain and 15% neuropathic or mixed pain. The pain is strongly related to pain at rest rather than that in motion.
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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.
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Increase in prophylaxis of glucocorticoid-induced osteoporosis by pharmacist feedback: a randomised controlled trial.
Klop, C, de Vries, F, Vinks, T, Kooij, MJ, van Staa, TP, Bijlsma, JW, Egberts, AC, Bouvy, ML
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2014;(1):385-92
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Abstract
UNLABELLED The aim of this study was to determine whether feedback by pharmacists to prescribers of patients eligible for glucocorticoid-induced osteoporosis prophylaxis would stimulate the prescribing of osteoporosis prophylaxis. The intervention did not significantly increase the prescribing of bisphosphonates in the total study population, but a significant increase was seen in men and in the elderly. However, the proportion of bisphosphonate-treated patients remained low. INTRODUCTION The aim of this study was to determine whether feedback by pharmacists to prescribers of patients eligible for glucocorticoid-induced osteoporosis prophylaxis (GIOP) would stimulate the implementation of the Dutch GIOP guideline. METHODS This randomised controlled trial included 695 patients who were dispensed ≥675 mg prednisone equivalents without a concomitant bisphosphonate prescription within 6 months before baseline. Pharmacists were asked to contact the physicians of GIOP-eligible patients in the intervention group to suggest osteoporosis prophylaxis. The primary endpoint was a bisphosphonate prescription. Secondary endpoints were a prescription of calcium supplements, vitamin D or any prophylactic osteoporosis drug (bisphosphonate, calcium supplements, vitamin D). RESULTS The group assigned to the intervention was slightly younger than the control group (68.7 ± 15.4 vs. 65.9 ± 16.9 years, p = 0.02) and used hydrocortisone more often (7.0% vs. 3.1%, p = 0.02). Within 6 months, the intervention did not significantly increase the prescribing of bisphosphonates (11.4% after intervention vs. 8.0% for controls; hazard ratio [HR] 1.47, 95% confidence interval [CI] 0.91-2.39). However, subgroup analyses showed a significant increase for the primary endpoint in men (12.8% vs. 5.1%, HR 2.53, 95% CI 1.11-5.74) and patients ≥70 years (13.4% vs. 4.9%, HR 2.88, 95% CI 1.33-6.23). The prescribing of calcium and vitamin D was not significantly altered. CONCLUSION This study showed that active identification of patients eligible for GIOP by pharmacists did not significantly increase the prescribing of bisphosphonates in the total study population, but there was an increase in men and the elderly. However, the proportion of GIOP-treated patients remained low.
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Intermittent zoledronic Acid prevents bone loss in adults after allogeneic hematopoietic cell transplantation.
Hari, P, DeFor, TE, Vesole, DH, Bredeson, CN, Burns, LJ
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2013;(9):1361-7
Abstract
Bone mineral density (BMD) loss is common in survivors of allogeneic hematopoietic cell transplantation (alloHCT). We performed a multicenter, phase II, randomized open-label trial of intravenous zoledronic acid (ZA) to prevent BMD loss in adult recipients of alloHCT with osteopenia before HCT. The treatment group received ZA 4 mg intravenously within 28 days pre-HCT and at 3 and 6 months after HCT. Both treatment and control groups received calcium carbonate and vitamin D supplements. Of 61 patients, 32 were randomized to the ZA cohort and 29 to the control cohorts. More patients in the ZA group had an HCT comorbidity index high-risk score of ≥3 (50% versus 21%, P < .01). Baseline BMD, T-scores, serum osteocalcin, bone alkaline phosphatase, and urine N-telopeptide (UNTX) levels were similar in both cohorts. Thirty patients were evaluable for outcomes (11 from the treatment and 19 from the control group). At 12 months, subjects in the treatment group had an improvement in BMD at the femoral neck (mean change, .018 for ZA group versus -.054 for controls; P = .04) and a significant decline in levels of UNTX (-56 for ZA group versus -9 for control; P = .04) compared with baseline. ZA was well tolerated and not associated with any cases of osteonecrosis of jaw or renal impairment. Lower survival observed in the ZA cohort was likely related to baseline imbalance in HCT-CI scores. Intermittent ZA is effective in preserving long-term bone health in adult alloHCT recipients at risk for osteoporosis.
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A 1-year randomized, double-blind, placebo-controlled study of intravenous ibandronate on bone loss following renal transplantation.
Smerud, KT, Dolgos, S, Olsen, IC, Åsberg, A, Sagedal, S, Reisæter, AV, Midtvedt, K, Pfeffer, P, Ueland, T, Godang, K, et al
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2012;(12):3316-25
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Abstract
The clinical profile of ibandronate as add-on to calcitriol and calcium was studied in this double-blind, placebo-controlled trial of 129 renal transplant recipients with early stable renal function (≤ 28 days posttransplantation, GFR ≥ 30 mL/min). Patients were randomized to receive i.v. ibandronate 3 mg or i.v. placebo every 3 months for 12 months on top of oral calcitriol 0.25 mcg/day and calcium 500 mg b.i.d. At baseline, 10 weeks and 12 months bone mineral density (BMD) and biochemical markers of bone turnover were measured. The primary endpoint, relative change in BMD for the lumbar spine from baseline to 12 months was not different, +1.5% for ibandronate versus +0.5% for placebo (p = 0.28). Ibandronate demonstrated a significant improvement of BMD in total femur, +1.3% versus -0.5% (p = 0.01) and in the ultradistal radius, +0.6% versus -1.9% (p = 0.039). Bone formation markers were reduced by ibandronate, whereas the bone resorption marker, NTX, was reduced in both groups. Calcium and calcitriol supplementation alone showed an excellent efficacy and safety profile, virtually maintaining BMD without any loss over 12 months after renal transplantation, whereas adding ibandronate significantly improved BMD in total femur and ultradistal radius, and also suppressed biomarkers of bone turnover. Ibandronate was also well tolerated.
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Once-yearly zoledronic acid in older men compared with women with recent hip fracture.
Boonen, S, Orwoll, E, Magaziner, J, Colón-Emeric, CS, Adachi, JD, Bucci-Rechtweg, C, Haentjens, P, Kaufman, JM, Rizzoli, R, Vanderschueren, D, et al
Journal of the American Geriatrics Society. 2011;(11):2084-90
Abstract
OBJECTIVES To assess the efficacy of once-yearly zoledronic acid (ZOL) 5 mg in increasing bone mineral density (BMD) in men with a recent hip fracture participating in the Health Outcomes and Reduced Incidence with Zoledronic Acid Once- Yearly Recurrent Fracture Trial and to compare the efficacy with that in women from the same study. DESIGN Randomized, placebo-controlled, double-blind trial. SETTING International multicenter. PARTICIPANTS Five hundred and eight men and 1,619 women within 90 days of surgical repair of low-trauma hip fracture in the same study (for comparison). INTERVENTION Once-yearly intravenous (IV) ZOL 5 mg (n = 248) or placebo (n = 260), loading dose of vitamin D, daily calcium, and vitamin D supplements. MEASUREMENT Changes in BMD. RESULTS Percentage change from baseline in total hip BMD at Months 12 and 24 was significantly higher with ZOL than with placebo (between-group difference, 2.0%, P = .003, and 3.8%, P = .002, respectively). Percentage change from baseline in femoral neck BMD at Month 24 was significantly higher with ZOL than with placebo (3.8%, P = .003). The BMD benefit was comparable with that observed in women in this study. New clinical fractures occurred in 36 (7.1%) participants (ZOL, n = 16; placebo, n = 20; P = .64). The ZOL safety profile was comparable with that of placebo, with no significant differences in cardiovascular or long-term renal function and a trend toward lower mortality in ZOL-treated men. CONCLUSION Once-yearly IV ZOL 5 mg increases bone mass at the hip and femoral neck in men within 90 days of repair of a low-trauma hip fracture. Increases were of a similar magnitude to those observed in women in the same study.
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Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma.
Henry, DH, Costa, L, Goldwasser, F, Hirsh, V, Hungria, V, Prausova, J, Scagliotti, GV, Sleeboom, H, Spencer, A, Vadhan-Raj, S, et al
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2011;(9):1125-32
Abstract
PURPOSE This study compared denosumab, a fully human monoclonal anti-receptor activator of nuclear factor kappa-B ligand antibody, with zoledronic acid (ZA) for delaying or preventing skeletal-related events (SRE) in patients with advanced cancer and bone metastases (excluding breast and prostate) or myeloma. PATIENTS AND METHODS Eligible patients were randomly assigned in a double-blind, double-dummy design to receive monthly subcutaneous denosumab 120 mg (n = 886) or intravenous ZA 4 mg (dose adjusted for renal impairment; n = 890). Daily supplemental calcium and vitamin D were strongly recommended. The primary end point was time to first on-study SRE (pathologic fracture, radiation or surgery to bone, or spinal cord compression). RESULTS Denosumab was noninferior to ZA in delaying time to first on-study SRE (hazard ratio, 0.84; 95% CI, 0.71 to 0.98; P = .0007). Although directionally favorable, denosumab was not statistically superior to ZA in delaying time to first on-study SRE (P = .03 unadjusted; P = .06 adjusted for multiplicity) or time to first-and-subsequent (multiple) SRE (rate ratio, 0.90; 95% CI, 0.77 to 1.04; P = .14). Overall survival and disease progression were similar between groups. Hypocalcemia occurred more frequently with denosumab. Osteonecrosis of the jaw occurred at similarly low rates in both groups. Acute-phase reactions after the first dose occurred more frequently with ZA, as did renal adverse events and elevations in serum creatinine based on National Cancer Institute Common Toxicity Criteria for Adverse Events grading. CONCLUSION Denosumab was noninferior (trending to superiority) to ZA in preventing or delaying first on-study SRE in patients with advanced cancer metastatic to bone or myeloma. Denosumab represents a potential novel treatment option with the convenience of subcutaneous administration and no requirement for renal monitoring or dose adjustment.