Background: identification of individuals with high fracture risk from within primary care is complex. It is likely that the true contribution of falls to fracture risk is underestimated.
Methods: cross-sectional analysis of a population-based cohort of 3,200 post-menopausal women aged 73 ± 4 years. Self-reported data were collected on fracture, osteoporosis clinical risk factors and falls/mobility risk factors. Self-reported falls were compared with recorded falls on GP computerised records. Multivariable logistic regression was used to identify independent risk factors for fracture.
Results: a total of 838 (26.2%) reported a fracture after aged 50; 441 reported falling more than once per year, but 69% of these had no mention of falls on their computerised GP records. Only age [odds ratios (OR): 1.37 per 5 year increase, 95% confidence interval (CI): 1.23–1.53], height (1.02 per cm increase, 95% CI: 1.01–1.04), weight (OR: 0.99 per kg increase, 95% CI: 0.98–0.99) and falls (OR: 1.49 for more than once per year compared with less, 95% CI: 1.13–1.94) were independent risk factors for fracture. Falls had the strongest association.
Conclusion: when identifying individuals with high fracture risk we estimate that more than one fall per year is at least twice as important as height and weight. Furthermore, using self-reported falls data is essential as computerised GP records underestimate falls prevalence.
fractures; falls; COSHIBA; FRAX; cohort study; elderly
Vertebral fractures are a major adverse consequence of osteoporosis. In a large placebo-controlled trial in postmenopausal women with osteoporosis, strontium ranelate reduced vertebral fracture risk by 33% over 4 years, confirming the role of strontium ranelate as an effective long-term treatment in osteoporosis.
Osteoporotic vertebral fractures are associated with increased mortality, morbidity, and loss of quality-of-life (QoL). Strontium ranelate (2 g/day) was shown to prevent bone loss, increase bone strength, and reduce vertebral and peripheral fractures. The preplanned aim of this study was to evaluate long-term efficacy and safety of strontium ranelate.
A total of 1,649 postmenopausal osteoporotic women were randomized to strontium ranelate or placebo for 4 years, followed by a 1-year treatment-switch period for half of the patients. Primary efficacy criterion was incidence of patients with new vertebral fractures over 4 years. Lumbar bone mineral density (BMD) and QoL were also evaluated.
Over 4 years, risk of vertebral fracture was reduced by 33% with strontium ranelate (risk reduction = 0.67, p < 0.001). Among patients with two or more prevalent vertebral fractures, risk reduction was 36% (p < 0.001). QoL, assessed by the QUALIOST®, was significantly better (p = 0.025), and patients without back pain were greater (p = 0.005) with strontium ranelate than placebo over 4 years. Lumbar BMD increased over 5 years in patients who continued with strontium ranelate, while it decreased in patients who switched to placebo. Emergent adverse events were similar between groups.
In this 4- and 5-year study, strontium ranelate is an effective and safe treatment for long-term treatment of osteoporosis in postmenopausal women.
Bone densitometry; Menopause; Osteoporotic fracture; Osteoporosis treatment; Strontium ranelate
Bisphosphonates can reduce fracture risk in patients with osteoporosis, but many at-risk patients do not start or adhere to these medications. The aims of this study are to: (1) preliminarily evaluate the effect of an individualized 10-year osteoporotic fracture risk calculator and decision aid (OSTEOPOROSIS CHOICE) for postmenopausal women at risk for osteoporotic fractures; and (2) assess the feasibility and validity (i.e., absence of contamination) of patient-level randomization (vs. cluster randomization) in pilot trials of decision aid efficacy.
This is a protocol for a parallel, 2-arm, randomized trial to compare an intervention group receiving OSTEOPOROSIS CHOICE to a control group receiving usual primary care. Postmenopausal women with bone mineral density T-scores of <-1.0, not receiving bisphosphonate therapy, and receiving care at participating primary care practices in and around Rochester, Minnesota, USA will be eligible to participate in the trial. We will measure the effect of OSTEOPOROSIS CHOICE on five outcomes: (a) patient knowledge regarding osteoporosis risk factors and treatment; (b) quality of the decision-making process for both the patient and clinician; (c) patient and clinician acceptability and satisfaction with the decision aid; (d) rate of bisphosphonate use and adherence, and (e) trial processes (e.g., ability to recruit participants, collect patient outcomes). To capture these outcomes, we will use patient and clinician surveys following each visit and video recordings of the clinical encounters. These video recordings will also allow us to determine the extent to which clinicians previously exposed to the decision aid were able to recreate elements of the decision aid with control patients (i.e., contamination). Pharmacy prescription profiles and follow-up phone interviews will assess medication start and adherence at 6 months.
This pilot trial will provide evidence of feasibility, validity of patient randomization, and preliminary efficacy of a novel approach -- decision aids -- to improving medication adherence for postmenopausal women at risk of osteoporotic fractures. The results will inform the design of a larger trial that could provide more precise estimates of the efficacy of the decision aid.
Clinical Trials.gov Identifier: NCT00578981
To determine the efficacy of once-yearly intravenous zoledronic acid (ZOL) 5 mg in reducing risk of clinical vertebral, nonvertebral, and any clinical fractures in elderly osteoporotic postmenopausal women.
A post hoc subgroup analysis of pooled data from the Health Outcome and Reduced Incidence with Zoledronic Acid One Yearly (HORIZON) Pivotal Fracture Trial and the HORIZON Recurrent Fracture Trial.
Multicenter, randomized, double-blind, placebo-controlled trials.
Postmenopausal women (aged ≥75) with documented osteoporosis (T-score ≤ −2.5 at femoral neck or ≥1 prevalent vertebral or hip fracture) or a recent hip fracture.
Patients were randomized to receive an intravenous infusion of ZOL 5 mg (n =1,961) or placebo (n =1,926) at baseline and 12 and 24 months.
Primary endpoints were incidence of clinical vertebral and nonvertebral and any clinical fracture after treatment.
At 3 years, incidence of any clinical, clinical vertebral, and nonvertebral fracture were significantly lower in the ZOL group than in the placebo group (10.8% vs 16.6%, 1.1% vs 3.7%, and 9.9% vs 13.7%, respectively) (hazard ratio (HR) =0.65, 95% confidence interval (CI) =0.54–0.78, P<.001; HR =0.34, 95% CI =0.21–0.55, P<.001; and HR =0.73, 95% CI =0.60–0.90, P =.002, respectively). The incidence of hip fracture was lower with ZOL but did not reach statistical significance. The incidence rate of postdose adverse events were higher with ZOL, although the rate of serious adverse events and deaths was comparable between the two groups.
Once-yearly intravenous ZOL 5 mg was associated with a significant reduction in the risk of new clinical fractures (vertebral and nonvertebral) in elderly postmenopausal women with osteroporosis.
elderly; postmenopausal women with osteoporosis; fractures; zoledronic acid
A randomized placebo-controlled trial was conducted to examine the effect of daily oral 1 mg minodronate on vertebral fractures in 704 postmenopausal women with established osteoporosis for 24 months. Minodronate treatment reduced vertebral fractures by 59% without serious adverse events. Minodronate is a safe and effective bisphosphonate for osteoporosis treatment.
Minodronate increases bone mineral density (BMD) in postmenopausal osteoporotic patients. However, its efficacy in reducing osteoporotic fractures has not been tested.
To examine anti-fracture efficacy and safety of daily oral minodronate in postmenopausal women with established osteoporosis, a randomized, double-blind, placebo-controlled trial was conducted in 704 postmenopausal women (55 to 80 years) with one to five vertebral fractures and low BMD. Subjects were randomly assigned to receive daily oral 1 mg minodronate (n = 359) or placebo (n = 345) for 24 months, with daily supplements of 600 mg calcium and 200 IU vitamin D3.
Daily 1 mg minodronate for 24 months reduced the risk of vertebral fractures by 59% (95% CI, 36.6–73.3%). Furthermore, when fractures during the first 6 months were eliminated, the risk of vertebral fractures from 6 to 24 months was reduced by 74% in minodronate-treated group. Minodronate treatment also reduced height loss. Bone turnover markers were suppressed by about 50% after 6 months of minodronate treatment and remained suppressed thereafter. The overall safety profile including gastrointestinal safety was similar between the two groups.
Daily oral minodronate is safe, well-tolerated, and is effective in reducing vertebral fracture risk in postmenopausal women with established osteoporosis.
Bisphosphonate; Bone turnover markers; Fracture prevention; Height loss; Minodronate
Osteoporosis is a common skeletal disease characterized by a reduction in bone strength and increased risk of fractures. Osteoporotic fractures are associated with substantial morbidity, mortality, and high healthcare costs. Treatments for osteoporosis have been shown to increase bone strength and reduce fracture risk. The drugs most commonly used to treat osteoporosis are bisphosphonates: stable analogs of naturally occurring inorganic pyrophosphate. The bisphosphonates share a common chemical structure with side chain variations that convey differences in their pharmacological properties, such as affinity for bone mineral and inhibitory effect on osteoclastic bone resorption. The clinical profiles of bisphosphonates, such as time of onset and offset of effect, may differ according to these pharmacological properties. Bisphosphonates can be administered orally or intravenously with a wide range of doses and dosing intervals. Randomized placebo-controlled clinical trials have shown that bisphosphonates reduce fracture risk in postmenopausal women with osteoporosis and have a generally excellent safety record. Clinical challenges in using bisphosphonates to treat osteoporosis include appropriate selection of patients for initiating therapy, choosing which bisphosphonate to use, monitoring therapy to assure that medication is taken correctly and the desired effect is achieved, determining when drug discontinuation should be considered, and managing side effects, possible side effects, and fear of side effects. Strategies for treating patients with bisphosphonates should consider each of these issues.
benefit; bisphosphonate; efficacy; osteoporosis; treatment; risk; safety
The results of this study suggest that, under the assumption of same relative risk reduction of fractures in men as for women, strontium ranelate could be considered a cost-effective strategy compared with no treatment for the treatment of osteoporotic men from a Belgian healthcare payer perspective.
This study was conducted to estimate the cost-effectiveness of strontium ranelate in the treatment of osteoporotic men.
A previously validated Markov microsimulation model was adapted to estimate the cost (€2,010) per quality-adjusted life-year (QALY) gained of strontium ranelate compared with no treatment. Similar efficacy data on lumbar spine and femoral neck bone mineral density (BMD) between men with osteoporosis at high risk of fracture (MALEO Trial) and postmenopausal osteoporotic women (pivotal SOTI, TROPOS trials) supports the assumption, in the base-case analysis, of the same relative risk reduction of fractures in men as for women. Analyses were conducted, from a Belgian healthcare payer perspective, in the population from the MALEO Trial who is a men population with a mean age of 73 years, and BMD T-score ≤−2.5 or prevalent vertebral fracture (PVF).
In the MALEO population, strontium ranelate compared with no treatment was estimated at €49,798 and €25,584 per QALY gained using efficacy data from the intent-to-treat analysis and the per-protocol analysis including only adherent patients, respectively. In men with a BMD T-score ≤−2.5 or with PVF, the cost per QALY gained of strontium ranelate fall below thresholds of €45,000 and €25,000 per QALY gained based on efficacy data from the entire population of the clinical trial and from the per-protocol analyses, respectively.
The results of this study suggest that, under the assumption of same relative risk reduction of fractures in men as for women, strontium ranelate could be considered cost-effective compared with no treatment for male osteoporosis.
Cost-effectiveness; Fractures; Men; Osteoporosis; Strontium ranelate
To identify high-risk patients and provide pharmacological treatment is one of the effective approaches in prevention of osteoporotic fractures. This study investigated the effect of 12-month Alendronate treatment on bone mineral density (BMD) and bone turnover biochemical markers in postmenopausal women with one or more non-traumatic fractures, i.e. patients with established osteoporosis.
A total of 118 Hong Kong postmenopausal Chinese women aged 50 to 75 with low-energy fracture at distal radius (Colles' fracture) were recruited for BMD measurement at lumbar spine and non-dominant hip using Dual-Energy X-ray Absorptiometry (DXA). 47 women with BMD T-score below -2 SD at either side were identified as patients with established osteoporosis and then randomized into Alendronate group (n = 22) and placebo control group (n = 25) for BMD measurement at spine and hip using DXA and distal radius of the non-fracture side by peripheral quantitative computed tomography (pQCT), and bone turnover markers, including bone forming alkaline phosphatase (BALP) and bone resorbing urinary Deoxypyridinoline (DPD). All measurements were repeated at 6 and 12 months.
Alendronate treatment significantly increased BMD, more in weight-bearing skeletons (5.1% at spine and 2.5% at hip) than in non-weight bearing skeleton (0.9% at distal radius) after 12 months treatment. Spine T-score was significant improved in Alendronate group (p < 0.01) (from -2.2 to -1.9) but not in control placebo group. The Alendronate treatment effect was explained by significant suppression of bone turnover.
12 months Alendronate treatment was effective to increase BMD at both axial and appendicular skeletons in postmenopausal women with established osteoporosis.
Early osteoporotic fractures have a great impact on disease progression, the first fracture being a major risk factor for further fractures. Strontium ranelate efficacy against vertebral fractures is presently assessed in a subset of women aged 50–65 years.
The Spinal Osteoporosis Therapeutic Intervention (SOTI) was an international, double blind, placebo controlled trial, supporting the efficacy of strontium ranelate 2 g/day in reducing the risk of vertebral fractures in postmenopausal women with osteoporosis and a prevalent vertebral fracture. 353 of these randomly assigned women were included in this analysis.
Over 4 years, strontium ranelate significantly reduced the risk of vertebral fracture by 35% (relative risk 0.65; 95% CI 0.42 to 0.99, p<0.05). In the strontium ranelate group, the bone mineral density increased from baseline by 15.8% at lumbar spine and 7.1% at femoral neck.
These data demonstrate a significant vertebral antifracture efficacy of strontium ranelate in young postmenopausal women aged 50–65 years with severe osteoporosis and confirm the efficacy of this antiosteoporotic treatment to prevent vertebral fractures, whatever the age of the patient.
It is known that bone mineral density (BMD) predicts the fracture's risk only partially and the severity and number of vertebral fractures are predictive of subsequent osteoporotic fractures (OF). Spinal deformity index (SDI) integrates the severity and number of morphometric vertebral fractures. Nowadays, there is interest in developing algorithms that use traditional statistics for predicting OF. Some studies suggest their poor sensitivity. Artificial Neural Networks (ANNs) could represent an alternative. So far, no study investigated ANNs ability in predicting OF and SDI. The aim of the present study is to compare ANNs and Logistic Regression (LR) in recognising, on the basis of osteoporotic risk-factors and other clinical information, patients with SDI≥1 and SDI≥5 from those with SDI = 0.
We compared ANNs prognostic performance with that of LR in identifying SDI≥1/SDI≥5 in 372 women with postmenopausal-osteoporosis (SDI≥1, n = 176; SDI = 0, n = 196; SDI≥5, n = 51), using 45 variables (44 clinical parameters plus BMD). ANNs were allowed to choose relevant input data automatically (TWIST-system-Semeion). Among 45 variables, 17 and 25 were selected by TWIST-system-Semeion, in SDI≥1 vs SDI = 0 (first) and SDI≥5 vs SDI = 0 (second) analysis. In the first analysis sensitivity of LR and ANNs was 35.8% and 72.5%, specificity 76.5% and 78.5% and accuracy 56.2% and 75.5%, respectively. In the second analysis, sensitivity of LR and ANNs was 37.3% and 74.8%, specificity 90.3% and 87.8%, and accuracy 63.8% and 81.3%, respectively.
ANNs showed a better performance in identifying both SDI≥1 and SDI≥5, with a higher sensitivity, suggesting its promising role in the development of algorithm for predicting OF.
Eldecalcitol, a vitamin D3 analogue, significantly reduces the risk of new vertebral fractures and increases bone mineral density (BMD) more than does alfacalcidol. To determine the effect of eldecalcitol on the incidence of all fragility fractures caused by osteoporosis, we conducted post hoc analyses of the phase III clinical trial to evaluate the incidence of the osteoporotic fractures defined in the World Health Organization (WHO) Technical Report, and, also, the incidence of the major osteoporotic fractures utilized in the WHO Fracture Risk Assessment Tool (FRAX), and compared those in the eldecalcitol group with those in the alfacalcidol group. We also analyzed the incidence of osteoporotic fractures stratified by prespecified risk factors for fractures. Eldecalcitol treatment reduced the incidence of osteoporotic fractures defined by the WHO more than alfacalcidol treatment (18.6 % vs. 25.2 %; hazard ratio, 0.70; 95 % CI, 0.54–0.93). Prevalent vertebral fractures, two or more prevalent vertebral fractures, and total hip BMD T score less than −2.5 were the risk factors for new osteoporotic fractures with significant differences between the two treatments. Eldecalcitol also decreased the incidence of major osteoporotic fractures in the FRAX more than alfacalcidol (11.1 % vs. 16.3 %; hazard ratio, 0.66; 95 % CI, 0.46–0.94). In conclusion, treatment with eldecalcitol reduced the risk of fragility fractures caused by osteoporosis compared with alfacalcidol administration, which may result from a potent effect of eldecalcitol on BMD, bone structure, and bone turnover.
Eldecalcitol; Fracture; FRAX; Osteoporosis; Vitamin D
Osteoporotic fractures are common and are associated with increased morbidity, mortality and health care costs. The most effective way to moderate increases in health care costs and the sickness and premature death associated with osteoporotic fractures, is to prevent osteoporosis. Several lines of evidence suggest that nitrates, drugs typically prescribed for the treatment of angina, may be effective in preventing postmenopausal osteoporosis.
We have designed a multicentre randomized controlled trial to determine the effects of nitrates on bone. The trial consists of two studies. The objective of the first study is to determine whether isosorbide mononitrate at 20 mg/day or nitroglycerin ointment at 15 mg/day leads to fewer headaches. The nitrate that is best tolerated will be used in a second study with one main objective: To determine if postmenopausal women with a T-score at the lumbar spine (L1 to L4) between 0 and -2.0 randomized to two years of treatment with intermittent nitrates have a greater increase in spine bone mineral density as compared to women randomized to placebo.
We hypothesize that: 1. Women will report fewer headaches when they are randomized to intermittent nitroglycerin ointment at 15 mg/day compared to intermittent oral isosorbide mononitrate at 20 mg/day, and, 2. After two years, women randomized to intermittent nitrates will have a greater percent increase in lumbar spine bone mineral density compared with women randomized to placebo.
We have completed our pilot study and found that transdermal nitroglycerin was associated with fewer headaches than oral isosorbide mononitrate. We are currently recruiting patients for our second main study.
The aim of the present study was to compare bone mineral density (BMD) and body composition (BC) measurements as well as identify risk factors for low BMD and osteoporotic fractures in postmenopausal women with psoriasis (Ps) and psoriatic arthritis (PsA).
A cross-sectional study was carried out in 45 PsA women, 52 Ps women and 98 healthy female controls (HC). Clinical risk factors for low bone density and osteoporotic fracture were evaluated by a specific questionnaire. An X-ray absorptiometry (DXA) at the lumbar spine, total femur and total body was performed on all patients. Skin and joint outcomes were measured by specific tools (PASI, HAQ and DAS28). Morphometric vertebral fractures were evaluated by lumbar and thoracic spine X-ray, according to Genant's method.
There were no significant differences in age, body mass index (BMI), total lean mass and bone mineral density among the groups. However, the PsA group had a significantly higher body fat percentage (BF%) than the Ps and HC groups. Osteoporotic fractures were more frequently observed in PsA and Ps groups than in the HC group (P = 0.01). Recurrent falls and a longer duration of disease increased the risk of fracture (odds ratio (OR) = 18.3 and 1.08, respectively) in the PsA group (P = 0.02). Disability was the main factor related to osteoporotic fracture in the Ps group (odds ratio (OR) = 11.1) (P = 0.02).
Ps and PsA patients did not present lower BMD. However, they had a higher prevalence of osteoporotic fractures and higher risk of metabolic syndrome. Patients with a longer duration of disease, disability and recurrent falls need preventive measures.
Within the PROF (Prevention of Osteoporotic Fractures) project, i.e. a synergistic effort of researchers and clinicians aimed at preventing osteoporotic fractures in Southern Apulia (Salento), we analysed the correlation between familial fragility fractures and osteopenic/osteoporotic status in postmenopausal women.
In the years 2009–2010, we screened 5665 postmenopausal women (mean age 62 years, range 39 to 86) by quantitative ultrasound testing, at the heel or phalanx. Demographic and anamnestic data were recorded for all the patients, including BMI, nutrition, menopause, physical activity, previous fractures, familial fragility fractures. Three demineralisation categories were identified a priori: Demineralisation, when any T-score <−1.0 SD was observed; b) Severe demineralisation, whenever a T-score <−2.0 was observed, corresponding to a higher risk of fracture; c) Osteoporosis, whenever a T-score <−2.5±0.2 (for the heel) or T-score <−3.2±0.2 (for the phalanx) was observed. Descriptive statistical analyses were performed in order to assess the correlation between familial fragility fractures (any osteoporotic fracture occurring in patients’ relatives) and the osteopenic or osteoporotic status of the patients themselves.
Demineralisation was observed in 4487 patients out of 5665 (79%). Demineralisation corresponding to severe osteopenia or osteoporotic status was confirmed in 2823 women (50% of all the examined subjects); 846 patients (15%) were found to be osteoporotic. A total of 358 women reported a family history of fragility fractures: of these, 298 (83%) presented demineralisation – as defined by T-score <−1 – corresponding at least to an osteopenic status. In the subgroup of women with familial fragility fractures, a status of severe osteopenia or osteoporosis was diagnosed in 191 patients (53%), with 76 of them being frankly osteoporotic (21%).
The PROF study dataset suggests that the presence of familial fragility fractures correlates with osteopenic and/or osteoporotic status in postmenopausal women. This finding may be regarded as a flag alerting both GPs and specialist physicians to the need for an integrated/preventive approach in the relatives of patients with fragility fractures.
Sub optimal levels of compliance and persistence with bisphosphonates are potentially compromising the reduction of post menopausal osteoporotic (PMO) fracture risk.
A structured literature search (1990–2006) was performed to identify primary research studies evaluating the relationship between compliance and persistence with bisphosphonates and post menopausal osteoporotic (PMO) fracture risk in clinical practice. Search criteria were: bisphosphonates; osteoporosis/osteopenia in postmenopausal women; all types of fractures; compliance and persistence.
Only two retrospective studies using prescription databases have specifically evaluated bisphosphonates.
A cohort study tracking 35,537 women reported that in those with a Medication Possession Ratio (MPR) of ≥80% over 24 months the risk of fracture was lower than in those with an MPR of <80% (8.5% v 10.7%, p < 0.001, Relative Risk Reduction (RRR) 21%). In women who persisted with treatment (refill gap <30 days) the risk of fracture was also lower (7.7% v 10.3%, p < 0.001, RRR 29%).
A nested case control study reported that 12 months persistence (refill gap <50% previous prescription (Rx) length) was associated with a 26% reduced risk of fracture (p < 0.05) and 24 months with a 32% reduced risk (p < 0.05).
Four other studies, not specific to bisphosphonates, reported that compliance ≥12 months decreased fracture risk by ~25%.
Sub optimal compliance and persistence with bisphosphonates is not providing the best possible protection against the risk of PMO fracture, however, more research is needed to delineate this relationship in clinical practice.
Vertebral fractures account for ~27% of all osteoporotic fractures in both men and women. The economic burden is substantial and growing: osteoporosis is expected to affect 14 million people by the year 2020. There is substantial morbidity associated with osteoporotic vertebral compression fractures (VCFs) including decreased quality of life, reduced pulmonary function, and increased mortality. Relatively recent additions to the treatment armamentarium include vertebral augmentation using vertebroplasty and kyphoplasty. Numerous retrospective and case studies demonstrate short-term efficacy and low complication rates of vertebroplasty and kyphoplasty in the treatment of osteoporotic VCFs, but controlled trials are needed for validation. The pathophysiology, risk factors, consequences, characteristics, and imaging of osteoporotic VCFs are presented in detail along with a discussion of treatment options and patient selection. Vertebral augmentation is comprehensively reviewed, including the technical aspects of the procedures, contraindications, complications, and clinical outcomes.
Vertebral compression fracture; vertebroplasty; kyphoplasty; osteoporosis; vertebral augmentation
Although osteoporosis is a systemic disease, vertebral fractures due to spinal bone loss are a frequent, sometimes early and often neglected complication of the disease, generally associated with considerable disability and pain. As osteoporotic vertebral fractures are an important predictor of future fracture risk, including at the hip, medical management is targeted at reducing fracture risk. A literature search for randomized, double-blind, prospective, controlled clinical studies addressing medical treatment possibilities of vertebral fractures in postmenopausal Caucasian women was performed on the leading medical databases. For each publication, the number of patients with at least one new vertebral fracture and the number of randomized patients by treatment arm was retrieved. The relative risk (RR) and the number needed to treat (NNT, i.e. the number of patients to be treated to avoid one radiological vertebral fracture over the duration of the study), together with the respective 95% confidence intervals (95%CI) were calculated for each study. Treatment of steroid-induced osteoporosis and treatment of osteoporosis in men were reviewed separately, based on the low number of publications available. Forty-five publications matched with the search criteria, allowing for analysis of 15 different substances tested regarding their anti-fracture efficacy at the vertebral level. Bisphosphonates, mainly alendronate and risedronate, were reported to have consistently reduced the risk of a vertebral fracture over up to 50 months of treatment in four (alendronate) and two (risedronate) publications. Raloxifene reduced vertebral fracture risk in one study over 36 months, which was confirmed by 48 months' follow-up data. Parathormone (PTH) showed a drastic reduction in vertebral fracture risk in early studies, while calcitonin may also be a treatment option to reduce fracture risk. For other substances published data are conflicting (calcitriol, fluoride) or insufficient to conclude about efficacy (calcium, clodronate, etidronate, hormone replacement therapy, pamidronate, strontium, tiludronate, vitamin D). The low NNTs for the leading substances (ranges: 15–64 for alendronate, 8–26 for risedronate, 23 for calcitonin and 28–31 for raloxifene) confirm that effective and efficient drug interventions for treatment and prevention of osteoporotic vertebral fractures are available. Bisphosphonates have demonstrated similar efficacy in treatment and prevention of steroid-induced and male osteoporosis as in postmenopausal osteoporosis. The selection of the appropriate drug for treatment of vertebral osteoporosis from among a bisphosphonate (alendronate or risedronate), PTH, calcitonin or raloxifene will mainly depend on the efficacy, tolerability and safety profile, together with the patient's willingness to comply with a long-term treatment. Although reduction of vertebral fracture risk is an important criterion for decision making, drugs with proven additional fracture risk reduction at all clinically relevant sites (especially at the hip) should be the preferred options.
Review; Medical treatment; Vertebral fractures; Osteoporosis; Relative risk reduction; Number needed to treat
The purpose of this study was to assess the cost-effectiveness of bazedoxifene and raloxifene for prevention of vertebral and nonvertebral fractures among postmenopausal Spanish women aged 55–82 years with established osteoporosis and a high fracture risk.
A Markov model was developed to represent the transition of a cohort of postmenopausal osteoporotic women through different health states, ie, patients free of fractures, patients with vertebral or nonvertebral fractures, and patients recovered from a fracture. Efficacy data for bazedoxifene were obtained from the Osteoporosis Study. The perspective of the Spanish National Health Service was chosen with a time horizon of 27 years. Costs were reported in 2010 Euros. Deterministic results were presented as expected cost per quality-adjusted life-year (QALY), and probabilistic results were represented in cost-effectiveness planes.
In deterministic analysis, the expected cost per patient was higher in the raloxifene cohort (€13,881) than in the bazedoxifene cohort (€13,436). QALYs gained were slightly higher in the bazedoxifene cohort (14.56 versus 14.54). Results from probabilistic sensitivity analysis showed that bazedoxifene has a slightly higher probability of being cost-effective for all threshold values independent of the maximum that the National Health Service is willing to pay per additional QALY.
Bazedoxifene was shown to be a cost-effective treatment option for the prevention of fractures in Spanish women with postmenopausal osteoporosis and a high fracture risk. When comparing bazedoxifene with raloxifene, it may be concluded that the former is the dominant strategy.
osteoporosis; bazedoxifene; raloxifene; vertebral; nonvertebral; fracture; efficacy; costs
Osteoporotic fractures are one of the major causes of increased morbidity and mortality in postmenopausal women and the overall aging population. One of the major issues in the management of postmenopausal osteoporosis is to find a safe and effective treatment in the long term (>3 years) to achieve and maintain a reduction in the risk of fracture. Strontium ranelate (PROTELOS®) is a relatively novel drug, currently approved in Europe for the treatment of postmenopausal osteoporosis. Strontium ranelate is the first agent of a new therapeutic class in osteoporosis, capable of both promoting bone formation and, to a lesser extent, inhibiting bone resorption. This uncoupling in bone turnover results in a net gain in bone mineral density (BMD), bone quality improvement and reduction in risk of vertebral and nonvertebral fractures, as initially demonstrated in the preplanned long-term registrative trials SOTI (Spinal Osteoporosis Therapeutic Intervention) and TROPOS (Treatment of Peripheral Osteoporosis) at 5 years. Recently, open-label extensions of the SOTI and TROPOS trials up to 8 and, recently, 10 years have confirmed the sustained efficacy of strontium ranelate in increasing BMD, the long-term safety profile and the high compliance to treatment, independently from baseline BMD or other risk factors for osteoporotic fractures. Recent economic impact analyses have proved that long-term treatment with strontium ranelate is highly cost effective, especially in women older than 70 years of age. Histomorphometric analyses in animals and humans participating in the phase III trials have proved that the quality of mineralization is preserved in the long term and bone microarchitecture is ameliorated, with increased bone strength. Thus, strontium ranelate has been confirmed to be an effective compound for the long-term, chronic treatment of postmenopausal osteoporosis.
anabolic; antiresorptive; bone formation; bone mineral density; bone resorption; mineralization; safety; tolerability
OBJECTIVES—Osteoporosis is a major cause of morbidity and cost. Patients sustaining one osteoporotic fracture are at increased risk of having another fracture. The objective of this study was to examine the use of "bone drugs" for the prevention of further osteoporotic fractures among patients who have had a "typical" osteoporotic fracture.
METHODS—This study took a random sample of 300 women aged 50 and over who had sustained either a vertebral, hip or Colles fracture in 1995 from the General Practice Research Database (GPRD) and compared their use of bone drugs with 300 age and practice matched controls.
RESULTS—Compared with age and practice matched control patients only vertebral fracture patients showed a statistically significant increase in the use of bone drugs in the year after fracture (39% and 2% for cases and controls respectively; 95% CI of difference 27% to 47%). Etidronate was the most commonly used compound.
CONCLUSION—The majority of patients sustaining an osteoporotic fracture are not prescribed any pharmaceutical agents for the secondary prevention of fracture one year after a primary fracture.
Keywords: osteoporosis; fracture
Osteoporotic post-menopausal women patients in two randomised trials comparing the anti-fracture efficacy of strontium ranelate with placebo were separated into tertiles according to their baseline levels of biochemical markers of bone formation and resorption. The vertebral anti-fracture efficacy of strontium ranelate was shown to be independent of baseline bone turnover levels.
Bone turnover (BTO) levels vary among women at risk of osteoporotic fracture. Strontium ranelate is an anti-osteoporotic treatment increasing bone formation and reducing bone resorption. It was hypothesised that its anti-fracture efficacy would be independent of baseline BTO levels.
Post-menopausal women with osteoporosis from two pooled studies were stratified in tertiles according to baseline levels of two BTO markers: bone-specific alkaline phosphatase (b-ALP, n = 4995) and serum C-telopeptide cross-links (sCTX, n = 4891). Vertebral fracture risk was assessed over 3 years with strontium ranelate 2 g/day or placebo.
In the placebo group, relative risk of vertebral fractures increased with BTO tertiles by 32% and 24% for patients in the highest tertile for b-ALP and CTX, respectively, compared to those in the lowest tertile. In the strontium ranelate group, incidences of vertebral fracture did not differ significantly across BTO tertiles. Significant reductions in vertebral fractures with strontium ranelate were seen in all tertiles of both markers, with relative risk reductions of 31% to 47% relative to placebo. Risk reduction did not differ among tertiles (b-ALP: p = 0.513; sCTX: p = 0.290).
The vertebral anti-fracture efficacy of strontium ranelate was independent of baseline BTO levels. Strontium ranelate offers clinical benefits to women across a wide range of metabolic states.
Anti-fracture efficacy; Biochemical marker; Bone turnover; Osteoporosis; Strontium ranelate; Vertebral fracture
Nursing home residents with a history of hip fractures or prior osteoporotic fractures were found to have an increased risk of another osteoporotic fracture over the ensuing two years when compared to nursing home residents with no fracture history.
Because of the high prevalence of osteoporosis and fall risk factors in nursing residents, it is possible that the importance of previous fracture as a marker for subsequent fracture risk may be diminished. We tested whether a history of prior osteoporotic fractures would identify residents at increased risk for additional fractures after nursing home admission.
We identified all Medicare enrollees age 50 and older who were in a nursing home North Carolina in 2000 (n=30,655). We examined Medicare hospitalization claims to determine which enrollees had been hospitalized in the preceding 4 years for a hip fracture (n=7,257) or other fracture (n=663). We followed subjects from their nursing home entry until the end of 2002 using Medicare hospital claims to determine which subjects were hospitalized with a subsequent fracture (n=3,381).
Among residents with no recent fracture history, 6.8% had a hospital claim for a subsequent fracture, while 15.1% of those with a prior non-hip fracture and 23.9% of subjects with a prior hip fracture sustained subsequent fractures. Multivariate proportional hazards models of time to fracture indicated that persons with prior hip fractures are at three times the risk (HR=2.99, 95% CI: 2.78, 3.21) and those hospitalized with other non-hip fractures are at 1.8 times the risk of subsequent fractures (HR=1.84, 95% CI: 1.50, 2.25).
Nursing home residents hospitalized with a prior osteoporotic fracture are at an increased risk of a fracture.
hip fracture; nursing home residents; osteoporosis; osteoporotic fractures
The aim of the study was to evaluate factors influencing quality of life (QOL) in Moroccan postmenopausal women with osteoporotic vertebral fracture assessed by the Arabic version of ECOS 16 questionnaire.
357 postmenopausal women were included in this study. The participants underwent bone mineral density (BMD) measurements by DXA of the lumbar spine and the total hip as well as X-ray examination of the thoraco-lumbar spine to identify subclinical vertebral fractures. Patients were asked to complete a questionnaire on clinical and sociodemographic parameters, and osteoporosis risk factors. The Arabic version of the ECOS16 (Assessment of health related quality of life in osteoporosis questionnaire) was used to assess quality of life.
The mean age was 58 ± 7.8 years, and the mean BMI was 28.3 ± 4.8 kg/m2. One hundred and eight women (30.1%) were osteoporotic and 46.7% had vertebral fractures. Most were categorized as Grade1 (75%). Three independent factors were associated with a poor quality of life: low educational level (p = 0,01), vertebral fracture (p = 0,03), and history of peripheral fracture (p = 0,006). Worse QOL was observed in the group with vertebral fracture in all domains except "pain": Physical functioning (p = 0,002); Fear of illness (p = 0,001); and Psychosocial functioning (p = 0,007). The number of fractures was a determinant of a low QOL, as indicated by an increased score in physical functioning (p = 0,01), fear of illness (p = 0,007), and total score (p = 0,01) after adjusting on age and educational level. Patients with higher Genant score had low QOL in these two domains too (p = 0,002; p = 0,001 respectively), and in the total score (p = 0,01) after adjusting on age and educational level.
Our current data showed that the quality of life assessed by the Arabic version of the ECOS 16 questionnaire is decreased in post menopausal women with prevalent vertebral fractures, with the increasing number and the severity of vertebral fractures.
Background: The markers of bone remodelling, such as serum osteocalcin, may be used to assess osteoporosis and to predict the fracture risk in elderly persons, especially in women. The bone mineral density which reflects the bone mass and strength, also predicts osteoporotic related hip fractures. So, this work highlights the association between the bone turnover and the bone mass and strength.
Aim: To assess the association between the biochemical markers of bone remodeling and osteocalcin with the bone mineral density in non osteoporotic and osteoporotic women among post menopausal subjects.
Materials and Methods: Sixty postmenopausal women whose ages ranged from 55-65 years included in this study, were further divided into group 1 (thirty non osteoporotic subjects) and group 2 (thirty osteoporotic subjects). For all the subjects, serum osteocalcin was measured by ELISA. BMD was measured by the Dual Energy X- Ray Absorptiometry (DXA) scan. The women with osteoporosis were diagnosed, based on the T- score of the bone mineral density, by the DXA scan. The Student’s “t” test was performed between the variables of both the groups and a correlation test was also performed between osteocalcin and BMD by using SPSS.
Results: A negative correlation was found between the osteocalcin level and the bone mineral density in post menopausal women. The mean values of both serum osteocalcin and BMD between the osteoporotic and the non osteoporotic subjects were statistically significant.
Conclusion: An increased bone turnover coincides with the trabecular deterioration in osteoporotic women of the post menopausal age group. A combination of biochemical markers and BMD may be a better predictor of the fracture risk than when it was assessed by either alone. The biochemical markers of the bone turnover cannot be a substitute for the serial BMD measurement, but they may be useful when they are considered in conjunction with the BMD measurement.
BMD; Osteocalcin; Osteoporosis
Vertebral fractures are the hallmark of osteoporosis, and occur with a higher incidence earlier in life than any other type of osteoporotic fractures. It has been shown that both symptomatic and asymptomatic vertebral fractures are associated with increased morbidity and mortality. Morbidity associated with these fractures includes decreased physical function and social isolation, which have a significant impact on the patient's overall quality of life. Since the majority of vertebral fractures do not come to clinical attention, radiographic diagnosis is considered to be the best way to identify and confirm the presence of osteoporotic vertebral fractures in clinical practice. Traditionally, conventional lateral radiographs of the thoracolumbar spine have been visually evaluated by radiologists or clinicians to identify vertebral fractures. The two most widely used methods to determine the severity of such fractures in clinical research are the semiquantitative assessment of vertebral deformities, which is based on visual evaluation, and the quantitative approach, which is based on different morphometric criteria. In our practice for osteoporosis evaluation we use the Genant semiquantitative approach: an accurate and reproducible method tested and applied in many clinical studies. The newest generation of fan-beam DXA systems delivering "high-resolution" lateral spine images offers a potential practical alternative to radiographs for clinical vertebral fracture analysis. The advantages of using DXA over conventional radiographic devices are its minimal radiation exposure and high-speed image acquisition. It also allows combined evaluation of vertebral fracture status and bone mass density, which could become a standard for patient evaluation in osteoporosis. The disadvantage of DXA use is that upper thoracic vertebrae cannot be evaluated in a substantial number of patients due to poor imaging quality. We truly believe that the that there is a major role for radiologists and clinicians alike to carefully assess and diagnose vertebral fractures using standardized grading schemes such as the one outlined in this review. Quantitative morphometry is useful in the context of epidemiological studies and clinical drug trials; however, the studies would be flawed if quantitative morphometry were to be performed in isolation without additional adjudication by a trained and highly experienced radiologist or clinician.
Osteoporosis; Vertebral fractures; Semiquantitative assessment; Bone mineral density; Quantitative morphometry