Osteoporosis is a growing public health problem and several drugs have been developed in the past two decades to offer pharmacological solutions both in prevention and in therapy. Alendronate was the first compound registered as an anti-fracture agent and also the most prescribed drug worldwide for osteoporosis. Patient compliance is a major problem with alendronate, with studies demonstrating that 50-60% of patients discontinue treatment within one year. Dysphagia and swallowing difficulties are common especially among elderly people and the perceived potential for upper GI problems is a barrier to good long-term adherence. As non-persistence and non-compliance are linked to increased risk of fractures, efforts have been made to develop forms of alendronate which are more acceptable to patients. Among these, the drinkable formulations have the potential great convenience, simplicity of administration and reduction in gastro-intestinal side effects. In addition these novel soluble products are equivalent in cost to generic alendronate tablets. The approaches to improve adherence to an old and effective medication for osteoporotic patients will be reviewed in this report, with a special focus on the recently marketed product Bonasol 70 mg oral solution.

A bone fractures only when loaded beyond its strength. The purpose of this study was to determine the association of femoral strength, as estimated by finite element (FE) analysis of dual-energy X-ray absorptiometry (DXA) scans, with incident hip fracture in comparison to hip bone mineral density (BMD), Fracture Risk Assessment Tool (FRAX), and hip structure analysis (HSA) variables. This prospective case-cohort study included a random sample of 1941 women and 668 incident hip fracture cases (295 in the random sample) during a mean ± SD follow-up of 12.8 ± 5.7 years from the Study of Osteoporotic Fractures (n = 7860 community-dwelling women ≥67 years of age). We analyzed the baseline DXA scans (Hologic 1000) of the hip using a validated plane-stress, linear-elastic finite element (FE) model of the proximal femur and estimated the femoral strength during a simulated sideways fall. Cox regression accounting for the case-cohort design assessed the association of estimated femoral strength with hip fracture. The age-body mass index (BMI)-adjusted hazard ratio (HR) per SD decrease for estimated strength (2.21; 95% CI, 1.95-2.50) was greater than that for total hip (TH) BMD (1.86; 95% CI, 1.67-2.08; p < 0.05), FN BMD (2.04; 95% CI, 1.79-2.32; p > 0.05), FRAX scores (range, 1.32-1.68; p < 0.0005), and many HSA variables (range, 1.13-2.43; p < 0.005), and the association was still significant (p < 0.05) after further adjustment for hip BMD or FRAX scores. The association of estimated strength with incident hip fracture was strong (Harrell's C index 0.770), significantly better than TH BMD (0.759; p < 0.05) and FRAX scores (0.711-0.743; p < 0.0001), but not FN BMD (0.762; p > 0.05). Similar findings were obtained for intracapsular and extracapsular fractures. In conclusion, the estimated femoral strength from FE analysis of DXA scans is an independent predictor and performs at least as well as FN BMD in predicting incident hip fracture in postmenopausal women.

© 2015 .Within each sex, there is an association between hip fracture risk and the size of the proximal femur, with larger femurs apparently more susceptible to fracture. Here, we investigate whether the thickness and density of the femoral cortex play a r

© 2015 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research. © 2015 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on

Background

The practice of a surgeon performing procedures in two operating rooms during overlapping time frames has been described as concurrent surgery if critical portions occur simultaneously, or overlapping surgery if they do not. Although recent media reports have focused on the potential adverse effects of these practices, to our knowledge, there has been no previous research investigating outcomes of overlapping procedures in orthopaedic surgery.

Methods

A retrospective review of an institutional clinical database from 2012 to 2015 was utilized to collect data from all surgical cases (including sports medicine, hand, and foot and ankle) performed at an ambulatory orthopaedic surgery center. Patient demographic characteristics, types of procedures, operating room time, procedure time, and 30-day outcomes including complications, unplanned hospital readmissions, unplanned reoperations, and emergency department visits were collected. The amount of overlap time between cases was also analyzed. Pearson chi-square tests, Student t tests, and logistic regression were used for statistical analysis.

Results

Of 3,640 cases performed, 68% were overlapping procedures and 32% were non-overlapping. There was no difference in the mean age, sex, body mass index, American Society of Anesthesiologists rating, or Charlson Comorbidity Index between patients who had overlapping procedures and those who did not. Comparison of overlapping surgery cases and non-overlapping surgery cases revealed no difference in the mean procedure time (70.7 minutes compared with 72.8 minutes; p = 0.116) or total operating room time (105.4 minutes compared with 105.5 minutes; p = 0.949). Complications were tracked for 30 days after procedures and yielded a rate of 1.1% for overlapping surgeries and 1.3% for non-overlapping surgeries (p = 0.811). Stratification based on subspecialty surgery also demonstrated no difference in complications between the cohorts. Fifty percent of overlapping cases overlapped by <1 hour of operating room time, but 7% overlapped by >2 hours. The rate of complications was found to have no association with the amount of overlap between cases (p = 0.151).

Conclusions

Overlapping surgery yields equivalent patient operating room time, procedure time, and 30-day complication rates as non-overlapping surgery in the ambulatory orthopaedic setting. Further investigation is warranted for inpatient orthopaedic procedures and across all orthopaedic subspecialties.

Level of evidence

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

A significant link between cardiovascular disease and osteoporosis is established in postmenopausal women, but data for men are scarce. We tested the hypothesis that greater severity of abdominal aortic calcification (AAC) was associated with an increased risk of nonspine fracture in 5994 men aged ≥ 65 years. AAC was assessed on 5400 baseline lateral thoracolumbar radiographs using a validated visual semiquantitative score. Total hip bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry. Incident nonspine fractures were centrally adjudicated. After adjustment for age, body mass index (BMI), total hip BMD, fall history, prior fracture, smoking status, comorbidities, race, and clinical center, the risk of nonspine fracture (n=805) was increased among men with higher AAC (hazard ratio [HR] quartile 4 [Q4] [AAC score ≥ 9] versus quartile 1 [Q1] [0-1], 1.36; 96% confidence interval [CI], 1.10-1.68). This association was due to an increased risk of hip fracture (n=178) among men with higher AAC (HR Q4 versus Q1, 2.33; 95% CI, 1.41-3.87). By contrast, the association between AAC and the risk of nonspine, nonhip fracture was weaker and not significant (HR Q4 versus Q1, 1.22; 95% CI, 0.96-1.55). The findings regarding higher AAC and increased risk of fracture were not altered in additional analyses accounting for degree of trauma, estimated glomerular filtration rate, presence of lumbar vertebral fractures (which may bias AAC assessment), preexisting cardiovascular disease, ankle brachial index, or competing risk of death. Thus, in this large cohort of elderly men, greater AAC was independently associated with an increased risk of hip fracture, but not with other nonspine fractures. These findings suggest that AAC assessment may be a useful method for identification of older men at high risk of hip fracture.

Importance

Discontinuation of bisphosphonate therapy after 3 to 5 years is increasingly considered, but methods to monitor fracture risk after discontinuation have not been established.

Objective

To test methods of predicting fracture risk among women who have discontinued alendronate therapy after 4 to 5 years.

Design, setting, and participants

The prospective Fracture Intervention Trial Long-term Extension (FLEX) study randomized postmenopausal women aged 61 to 86 years previously treated with 4 to 5 years of alendronate therapy to 5 more years of alendronate or placebo from 1998 through 2003; the present analysis includes only the placebo group. Hip and spine dual-energy x-ray absorptiometry (DXA) were measured when placebo was begun (FLEX baseline) and after 1 to 3 years of follow-up. Two biochemical markers of bone turnover, urinary type 1 collagen cross-linked N-telopeptide (NTX) and serum bone-specific alkaline phosphatase (BAP), were measured at FLEX baseline and after 1 and 3 years.

Main outcomes and measures

Symptomatic spine and nonspine fractures occurring after the follow-up measurement of DXA or bone turnover.

Results

During 5 years of placebo, 94 of 437 women (22%) experienced 1 or more symptomatic fractures; 82 had fractures after 1 year. One-year changes in hip DXA, NTX, and BAP were not related to subsequent fracture risk, but older age and lower hip DXA at time of discontinuation were significantly related to increased fracture risk (lowest tertile of baseline femoral neck DXA vs other 2 tertiles relative hazard ratio, 2.17 [95% CI, 1.38-3.41]; total hip DXA relative hazard ratio, 1.87 [95% CI, 1.20-2.92]).

Conclusions and relevance

Among postmenopausal women who discontinue alendronate therapy after 4 to 5 years, age and hip BMD at discontinuation predict clinical fractures during the subsequent 5 years. Follow-up measurements of DXA 1 year after discontinuation and of BAP or NTX 1 to 2 years after discontinuation are not associated with fracture risk and cannot be recommended.

Trial registration

clinicaltrials.gov Identifier: NCT00398931.

Purpose

To estimate how much the improvement in bone mass accounts for the reduction in risk of vertebral fracture that has been observed in randomized trials of antiresorptive treatments for osteoporosis.

Methods

After a systematic search, we conducted a meta-analysis of 12 trials to describe the relation between improvement in spine bone mineral density and reduction in risk of vertebral fracture in postmenopausal women. We also used logistic models to estimate the proportion of the reduction in risk of vertebral fracture observed with alendronate in the Fracture Intervention Trial that was due to improvement in bone mineral density.

Results

Across the 12 trials, a 1% improvement in spine bone mineral density was associated with a 0.03 decrease (95% confidence interval [CI]: 0.02 to 0.05) in the relative risk (RR) of vertebral fracture. The reductions in risk were greater than predicted from improvement in bone mineral density; for example, the model estimated that treatments predicted to reduce fracture risk by 20% (RR = 0.80), based on improvement in bone mineral density, actually reduce the risk of fracture by about 45% (RR = 0.55). In the Fracture Intervention Trial, improvement in spine bone mineral density explained 16% (95% CI: 11% to 27%) of the reduction in the risk of vertebral fracture with alendronate.

Conclusion

Improvement in spine bone mineral density during treatment with antiresorptive drugs accounts for a predictable but small part of the observed reduction in the risk of vertebral fracture.

An ASBMR Task Force recommends a drug holiday for certain women treated for ≥5 years with oral alendronate or ≥3 years with intravenous zoledronic acid, with reassessment 2 to 3 years later. It is not known whether changes in bone mineral density (BMD) or bone turnover markers differ after oral or intravenous therapy. Our goal was to compare changes in BMD and procollagen type I N propeptide (PINP) after oral or intravenous bisphosphonate use. In the Fracture Intervention Trial Long-term Extension (FLEX), women who received a mean 5 years of alendronate were randomized to placebo or continued treatment. In the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly-Pivotal Fracture Trial Extension I (HORIZON-PFT E1), women who received 3 years of zoledronic acid were randomized to placebo or continued treatment. We examined the proportion of participants with BMD loss or PINP gain ≥ least significant change (LSC) and those whose values exceeded a threshold (T-score ≤-2.5 or PINP ≥36.0 ng/mL, a premenopausal median value). After 3 years of placebo, the FLEX group had greater mean total hip BMD decreases (-2.3% versus -1.2% in the HORIZON-PFT E1 group, p < 0.01) and greater rises in PINP (+11.6 ng/mL versus +6.7 ng/mL, p < 0.01). There was a greater proportion of individuals in FLEX with total hip BMD loss and PINP increases that exceeded LSC, and PINP values ≥36.0 ng/mL. In contrast, there were small changes in the proportion of women with femoral neck T-scores ≤-2.5 in both groups. In conclusion, 3 years after bisphosphonate discontinuation, a considerable proportion of former alendronate and zoledronic acid users had meaningful declines in total hip BMD and elevations in PINP. Despite a longer treatment course, alendronate may have a more rapid offset of drug effect than zoledronic acid. © 2018 American Society for Bone and Mineral Research.