Potential cost-effective use of spine radiographs to detect vertebral deformity and select osteopenic post-menopausal women for amino-bisphosphonate therapy

Prevalent vertebral deformities are predictive of future clinical fractures independent of bone density. We used a Markov model with eight health states to estimate from the societal perspective the cost-effectiveness of using spine radiographs to identify postmenopausal women age 60 or older with one or more vertebral deformities and then treat them with anti-resorptive drug therapy to prevent fractures. We compared three strategies: 5 years of amino-bisphosphonate (alendronate) therapy for all, 5 years of alendronate therapy for only those with prevalent a radiographic vertebral deformity or no initial alendronate treatment. Lifetime direct medical and indirect costs, quality adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) were tracked. For women with one or more prevalent vertebral deformities, the costs per QALY gained ranged from $5,084 (for an 80 year old with a T-score of –2.4) to $61,192 (for a 60 year old with a T-score of –1.0). For women without prevalent vertebral deformity, the costs per QALY gained ranged from $41,897 (for a 60 year old with a T-score of –2.4) to $166,219 (for an 80 year old with a T-score of –1.0). These results were modestly sensitive to reasonable changes in fracture rates, disutility, discount rates and assumptions about the accuracy of spinal radiographs for detecting vertebral deformity. Assuming a societal willingness to pay per QALY gained of $50,000, the strategy of performing spine radiographs in post-menopausal osteopenic women with T-scores at or below –1.5 and treating those with 1 or more prevalent vertebral deformities is likely to be cost-effective. However, further research on the accuracy of vertebral deformity ascertainment from routine clinical radiographs and on the efficacy of amino-bisphosphonate drugs for reducing the risk of non-vertebral fractures in osteopenic women is needed to define more precisely the subset of osteopenic post-menopausal women in whom use of spinal radiographs is most cost-effective.     

Effects of risedronate on fracture risk in postmenopausal women with osteopenia

Summary This posthoc analysis of four trials studied the efficacy of risedronate to reduce fragility fractures in postmenopausal women with osteopenia (i.e., T-scores between −1 and −2.5). Risedronate reduced the fracture risk by 73% (p = 0.023) in this population of women with low femoral neck bone mass and no prevalent vertebral fractures. Introduction Low bone mass represents an increasing health risk and burden. Half of fragility fractures occur in osteopenic women underscoring the need for treatments reducing fracture risk. This analysis reports the effect of risedronate to reduce fragility fracture risk in osteopenic women without prevalent vertebral fractures. Methods Postmenopausal women with osteopenia, defined as femoral neck T-score between −1 and −2.5 by DXA and no prevalent vertebral fractures, were identified from four controlled randomized trials (BMD Multinational, BMD North America, VERT Multinational and VERT North America). The risk reduction for fragility fractures in patients receiving 5 mg risedronate daily for 1.5 to 3 years compared to placebo was assessed. An additional sensitivity analysis excluded patients who were osteopenic at the femoral neck but had a BMD lower than −2.5 SD at the lumbar spine. Results Six hundred and twenty postmenopausal women with osteopenia were included, receiving either placebo (n = 309) or risedronate 5 mg (n = 311). Risedronate reduced the risk of fragility fractures by 73% over 3 years versus placebo (p = 0.023); cumulative fragility fracture incidence was 6.9% in placebo-treated versus 2.2% in risedronate-treated patients. The magnitude of the effect was similar in the sensitivity analysis subset. Conclusion Risedronate significantly reduced the risk of fragility fractures in postmenopausal women with osteopenia (femoral neck T-score between −1 and −2.5 SD) and no prevalent vertebral fractures.     

Cost-effectiveness of vertebral fracture assessment to detect prevalent vertebral deformity and select postmenopausal women with a femoral neck T-score>-2.5 for alendronate therapy: a modeling study.

Most fractures occur in postmenopausal women who do not have osteoporosis by bone density criteria (T-score>-2.5). Prevalent vertebral deformity is a strong risk factor for incident fractures independent of bone mineral density, yet the majority of these deformities are clinically unapparent. Spine imaging on a dual-energy densitometer, called vertebral fracture assessment (VFA), can accurately detect these deformities. The purpose of this modeling study was to estimate the lifetime societal costs and health benefits of VFA and confirmatory follow-up radiography to detect prevalent vertebral deformity in osteopenic (T-score -1.5, -2.0, or -2.4) postmenopausal women, followed by anti-resorptive drug therapy for those with one or more deformities. We compared three strategies; no initial drug therapy, 5 yr of initial alendronate therapy, or VFA followed by 5 yr of alendronate therapy in those with one or more vertebral deformities confirmed on radiography (VFA strategy). Results for the base-case analyses showed that the cost per quality adjusted life year (QALY) gained for the VFA strategy relative to no initial drug therapy ranged from 18,000 US dollars (for a 60-yr-old with a femoral neck T-score of -2.4) to 77,000 US dollars (for an 80-yr-old with a T-score of -1.5). VFA with selective confirmatory radiography is cost-effective, assuming a societal willingness to pay per QALY gained of 50,000 US dollars, for postmenopausal women aged 60 to 80 yr with femoral neck T-scores between -2.0 and -2.4, and for women age 60 or 70 yr with a T-score of -1.5. Assuming a societal willingness to pay of 100,000 US dollars per QALY gained, VFA is also cost-effective for women age 80 yr with a T-score of -1.5. These conclusions are robust to reasonable changes in fracture rates, assumed fracture disutility, discount rates, relative risk of fracture attributable to vertebral deformity, alendronate cost, and drug adherence.     

Can the WHO definition of osteoporosis be applied to multi-site axial transmission quantitative ultrasound?

Osteoporosis is a highly prevalent but preventable disease and, as such, it is important that there are appropriate diagnostic criteria to identify those at risk of low trauma fracture. In 1994 the World Health Organization (WHO) introduced definitions of osteoporosis and osteopenia using T-scores, which identified 30% of all Caucasian post-menopausal women as having osteoporosis. However, the use of the WHO T-score thresholds of –2.5 for osteoporosis and –1.0 for osteopenia may be inappropriate at skeletal sites other than the spine, hip and forearm or when other modalities, such as quantitative ultrasound (QUS) are used. The aim of this study was to evaluate the age-dependence of T-scores for speed of sound (SOS) measurements at the radius, tibia, phalanx and metatarsal by use of the Sunlight Omnisense, to evaluate the prevalence of osteoporosis and osteopenia at these sites by use of the WHO criteria, and calculate appropriate equivalent T-score thresholds. The study population consisted of 278 healthy pre-menopausal women, 194 healthy post-menopausal women and 115 women with atraumatic vertebral fractures. All women had SOS measurements at the radius, tibia, phalanx and metatarsal and bone mineral density (BMD) measurements at the lumbar spine and hip. A group of healthy pre-menopausal women aged 20–40 years from the pre-menopausal group were used to estimate the population mean and SD for each of the SOS and BMD measurement sites. Healthy post-menopausal women were classified into normal, osteopenic or osteoporotic, based upon the standard WHO definition of osteoporosis and expressed as a percentage. We investigated the age-related decline in T-scores from 20–79 by stratifying the healthy subjects into 10-year age groups and calculating the mean T-score for each of these groups. Finally, we estimated appropriate T-score thresholds, using five different approaches. The prevalence of osteoporosis in the post-menopausal women aged 50 years and over ranged from 1.4 to 12.7% for SOS and 1.3 to 5.2% for BMD. The age-related decline in T-scores ranged from –0.92 to –1.80 for SOS measurements in the 60 to 69-year age group and –0.60 to –1.19 for BMD measurements in the same age group. The WHO definition was not suitable for use with SOS measurements, and revised T-score thresholds for the diagnosis of osteoporosis of –2.6, –3.0, –3.0 and –2.2 and for osteopenia of –1.4, –1.6, –2.3, and –1.4, for the radius, tibia, phalanx and metatarsal, respectively, were recommended.     

Risk of hip fracture after bisphosphonate discontinuation: implications for a drug holiday

Summary  Based upon interest in a bisphosphonate drug holiday, we evaluate the risk for hip fracture after bisphosphonate discontinuation. Among women compliant with bisphosphonates for ≥2 years, the risk of hip fracture was increased after discontinuation, although with higher compliance and a longer duration of preceding bisphosphonate therapy, this risk was attenuated. Introduction  Recent data suggest that hip fracture risk was not significantly increased among women receiving 5 years of bisphosphonate therapy who were subsequently randomized to placebo. We studied older women compliant with bisphosphonates ≥2 years to evaluate the risk of hip fracture after bisphosphonate discontinuation. Methods  Using administrative databases from a large U.S. healthcare organization, we identified women initiating bisphosphonate therapy compliant (Medication Possession Ratio, MPR ≥66%) for 2 years. We examined the rate of hip fracture among women who discontinued bisphosphonates versus those who remained on therapy. Results  At 2 years, 9,063 women were eligible for analysis. Hip fracture incidence among women who discontinued bisphosphonates versus those who did not was 8.43 versus 4.67 per 1000 person years (p = 0.016). The adjusted hazard ratio of hip fracture per 90 days following discontinuation was 1.2 (1.1–1.3). For women with higher compliance at 2 years (MPR ≥80%) or compliant for 3 years, there were no significant differences in risk associated with discontinuation. Conclusions  The rate of hip fracture was increased among women compliant with bisphosphonate therapy for 2 years who subsequently discontinued, suggesting that discontinuation is not advisable under these conditions. This association was attenuated with higher compliance and a longer duration of previous bisphosphonate therapy. Funding This project was funded by Novartis Pharmaceuticals and the Arthritis Foundation. The investigators also receive support from the National Institutes of Health (AR053351, AR052361). The authors independently developed the analysis plan, extracted the data, conducted the analysis, and interpreted the results.     

The cost-effectiveness of risedronate in the treatment of osteoporosis: an international perspective

Introduction Risedronate, a bisphosphonate for treatment and prevention of osteoporosis, has been shown in several clinical trials to reduce the risk of fractures in postmenopausal women with osteoporosis. The cost-effectiveness of risedronate treatment has previously been evaluated within different country settings using different model and analysis approaches. The objective of this study was to assess the cost-effectiveness of risedronate in postmenopausal women in four European countries—Sweden, Finland, Spain, and Belgium—by making use of the same modelling framework and analysis setup. Methods A previously developed Markov cohort model for the evaluation of osteoporosis treatments was used to estimate the cost-effectiveness of risedronate treatment. For each country, the model was populated with local mortality, fracture incidence, and cost data. Hip fractures, clinical vertebral fractures, and wrist fractures were included in the model. Results The incremental cost per quality-adjusted life years (QALY) gained from a 5-year intervention with risedronate compared to “no intervention” in 70-year-old women at the threshold of osteoporosis [T-score = −2.5 based on National Health and Nutrition Examination Survey (NHANES) III data] and previous vertebral fracture was estimated to be €860, €19,532, €11,782, and €32,515 in Sweden, Finland, Belgium, and Spain, respectively. Among 70-year-old women at the threshold of osteoporosis without previous fracture the estimated cost per QALY gained ranged from €21,148 (Sweden) to €80,100 (Spain). The differences in cost-effectiveness between countries are mainly explained by different costs (fracture and treatment costs), fracture risks, and discount rates. Based on cost per QALY gained threshold values found in the literature, the study results indicated risedronate to be cost effective in the treatment of elderly women with established osteoporosis in all the included countries. Conclusions At a hypothetical threshold value of €40,000 per QALY gained, the results in this study indicate that risedronate is a cost-effective treatment in elderly women at the threshold of osteoporosis (i.e., a T-score of −2.5) with prevalent vertebral fractures in Sweden, Finland, Belgium, and Spain. Financial support was obtained via an unrestricted grant from The Alliance for Better Bone Health.     

Potential Clinical and Economic Impact of Nonadherence with Osteoporosis Medications

This study aims to estimate the potential clinical and economic implications of therapeutic adherence to bisphosphonate therapy. A validated Markov microsimulation model was used to estimate the impact of varying adherence to bisphosphonate therapy on outcomes (the number of fractures and the quality-adjusted life-years [QALYs]), health-care costs, and the cost-effectiveness of therapy compared with no treatment. Adherence was divided into persistence and compliance, and multiple scenarios were considered for both concepts. Analyses were performed for women aged 65 years with a bone mineral density T-score of −2.5. Health outcomes and the cost-effectiveness of therapy improved significantly with increasing compliance and/or persistence. In the case of real-world persistence and with a medical possession ratio (MPR; i.e., the number of doses taken divided by the number of doses prescribed) of 100%, the QALY gain and the number of fractures prevented represented only 48 and 42% of the values estimated assuming full persistence, respectively. These proportions fell to 27 and 23% with an MPR value of 80%. The costs per QALY gained, for branded bisphosphonates (and generic alendronate), were estimated at €19,069 (€4,871), €32,278 (€11,985), and €64,052 (€30,181) for MPR values of 100, 80, and 60%, respectively, assuming real-world persistence. These values were €16,997 (€2,215), €24,401 (€6,179), and €51,750 (€20,569), respectively, assuming full persistence. In conclusion, poor compliance and failure to persist with osteoporosis medications results not only in deteriorating health outcomes, but also in a decreased cost-effectiveness of drug therapy. Adherence therefore remains an important challenge for health-care professionals treating osteoporosis.     

Age and drug therapy are key prognostic factors for first clinical fracture in patients with primary osteoporosis

Summary We evaluated the characteristics of 1,142 women and men who attended Canadian osteoporosis clinics and had T-score ≤ −2.0 and no prior fractures to determine the predictors of first clinical fracture. Greater age and failure to start osteoporosis drug treatment increased the risk of first clinical fracture. Introduction Although risk factors for osteoporotic fractures are well-known, it is unclear which factors predict poor prognosis in patients with primary osteoporosis. The purpose of this study was to determine prognostic factors for first clinical fracture in patients with T-score ≤ −2.0 and no previous clinical fracture. Methods We examined prospectively collected data from 1,142 patients aged 40 and over in the Canadian Database of Osteoporosis and Osteopenia. We used prognosis methodology and performed survival analysis to determine factors that increase the risk of first clinical fracture. Results Our inception cohort (mean age = 60.6 years, 91% females) had a cumulative fracture incidence of 5.1% (incidence rate: 2.53/100 person-years). Age and osteoporosis drug use predicted incident clinical fractures in multivariable regression analyses. The risk of first fracture increased by 3% per year. Failing to initiate osteoporosis treatment increased fracture risk by 2.4 times. In addition, low physical activity, high body mass index and low T-scores were found to predict fracture risk in certain patient subgroups using tree-structured survival analysis. These findings were robust and did not change with most sensitivity analyses. Conclusion Age and osteoporosis drug treatment are the main prognostic predictors of first clinical fracture in patients with T-score ≤ −2.0. Dr. O. Gajic-Veljanoski was supported by an Ontario Women’s Health Council Master’s Level student award and Dr. AM Cheung is supported by a 5-year Mid-Career Award from Canadian Institutes of Health Research / Ontario Women’s Health Council and a Premier’s Research Excellence Award. The collection of data in CANDOO was supported by a series of unrestricted grants from the Alliance for Better Bone Health from 1994 to 2002. This study did not receive funding from pharmaceutical companies. It was performed to fulfill requirements of a Master’s degree thesis in clinical epidemiology at the University of Toronto.     

Assessment of the bone status of Nigerian women by ultrasound and biochemical markers

Ultrasound analysis of the calcaneus and serum markers of bone turnover were used to examine the bone status of healthy Nigerian women who reside in an area of the world where dietary calcium intake is generally low and estrogen replacement therapy is not widely available. A total of 218 women (108 premenopausal and 110 postmenopausal) between the ages of 16 and 95 years were enrolled in the study. Broadband ultrasound attenuation (BUA) and speed of sound velocity (SOS) were measured and used to calculate the stiffness index (SI) of the calcaneus. In this cross-sectional study, the Nigerian women exhibited a marked age-dependent decline in SI that was defined by the regression equation SI=105.9–6.62E-3×Age². SI was significantly correlated with age (r=−0.41,P<0.001) and with serum NTx concentrations (r=−0.26,P<0.001), but not with serum levels of bone specific alkaline phosphatase (BSAP). Years since menopause was also significantly correlated with SI (r=0.40,P<0.001). A significant increase in serum NTx concentration occurred at least a decade before a significant decline in SI was evident. In the total study group, 24% of the women had T-scores indicative of osteopenia and 9% had T-scores indicative of osteoporosis, based on US reference data. Although the reported current incidence of fracture is low in women in sub-Saharan West Africa, these data show that after menopause Nigerian women have a decline in bone quality and increase in bone turnover similar to North American Caucasian women.     

Outcomes after switching from one bisphosphonate to another in 146 patients at a single university hospital

Summary  Most patients who switched to a second bisphosphonate continued their treatment long term, although those who stopped their first drug because of adverse events were likely to discontinue the second drug for the same reason. Switching to another bisphosphonate is a reasonable treatment option for some patients with treatment failure. Introduction  Patients who experience treatment failure with a bisphosphonate because of adverse events (AEs) or other reasons might receive a second bisphosphonate. However, the frequency and benefits of switching bisphosphonates are unknown. Methods  We retrospectively evaluated 197 men and 1110 women newly treated with bisphosphonates between 1 January 2000 and 30 June 2005 at our university hospital. Results  Among the 497 patients who discontinued bisphosphonate treatment, 146 were switched to a second bisphosphonate. The cumulative probabilities of persistence of treatment after 3 years were 45% with the first bisphosphonate and 65% with the second (P = 0.017). Age ≥65 years, switching bisphosphonates because of AEs, and male gender were associated (P < 0.05) with low persistence of treatment with the second bisphosphonate. Discontinuation of the first drug because of AEs was associated with an increased rate of discontinuation of the second drug because of AEs (hazard ratio, 4.2; 95% confidence interval, 2.1–8.4). Conclusions  Patients who switched bisphosphonates had high rates of persistence of therapy. Those who stopped their first bisphosphonate because of AEs were at risk of discontinuing the second drug for the same reason. Switching to another bisphosphonate is a reasonable treatment option for some patients with treatment failure. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Effect of low-power gallium-aluminum-arsenium laser therapy (830 nm) in combination with bisphosphonate treatment on osteopenic bone structure: an experimental animal study

Laser therapy is able to modulate cell metabolism and accelerate the repair of fracture. Little attention has been given to the effect of laser on bone with osteopenia or osteoporosis. The purpose of our study was to verify the effect of laser therapy in combination with bisphosphonate on osteopenic bone structure. The 35 Wistar female rats used were divided into five groups: (1) sham-operation rats (control), (2) ovariectomized (OVX’d) rats with osteopenia, (3) OVX’d rats with osteopenia treated with laser, (4) OVX’d rats with osteopenia treated with bisphosphonate and (5) OVX’d rats with osteopenia treated with bisphosphonate and laser. Groups 3 and 5 were given daily 6 mg doses of bisphosphonate orally. Groups 4 and 5 underwent low level laser therapy [gallium-aluminum-arsenium (GaAlAs) laser, 830 nm, 50 mW and 4 J/cm²] on the femoral neck and vertebral segments (T13-L2). Both treatments were performed over an 8-week period. Rats from the osteopenic control and osteopenic + laser groups presented marked osteopenia. In the osteopenic + bisphosphonate group, the trabecular bone volume in vertebra L2 was significantly greater than in the osteopenic control group. Notably, in the association between laser and bisphosphonate, the trabecular bone volume was significantly greater in vertebrae L2 and T13 and was similar to that in the sham-operation control group. It was concluded that the laser therapy associated with bisphosphonate treatment was the best method for reversing vertebral osteopenia caused by the ovariectomy.     

Cost‐effectiveness of alendronate for the treatment of osteopenic postmenopausal women in Japan

Many postmenopausal women have osteopenia, a condition characterized by loss of bone mineral density (BMD) that is not as severe as in osteoporosis. The objective of this study was to estimate the cost‐effectiveness of alendronate to prevent fractures in osteopenic postmenopausal women without a history of fracture in Japan. An individual simulation model was developed to predict lifetime costs and quality‐adjusted life years (QALYs) of 5 years of preventive alendronate therapy versus no preventive therapy. The risk of hip and vertebral fracture associated with age and BMD was derived from epidemiologic studies in Japan. We ran the model with different combinations of age (65, 70, and 75 years), BMD (70%, 75%, and 80% of young adult mean [YAM]), and additional clinical risk factors. For 70‐year‐old women with a BMD of 70% of the YAM having one of the following risk factors: a family history of hip fracture, high alcohol intake, or current smoking, the incremental cost‐effectiveness ratio (ICER) of alendronate was $92,937, $126,251, and $129,067 per QALY, respectively. These results were sensitive to age, BMD, and number of clinical risk factors. Probabilistic sensitivity analysis for the base case showed that in the presence of one, two, and three risk factors, alendronate was cost‐effective in 0.2% to 2.6%, 13.1% to 56.1%, and 99.1% of the simulations, respectively, if society is willing to pay $50,000 per QALY. Additional analysis indicated that alendronate can be a good value in osteopenic women if the 10‐year probability for a osteoporotic hip or vertebral fracture is more than 26.2%. Our results indicate that whether to treat osteopenia with alendronate should be determined on the basis of age, BMD, and number of clinical risk factors in terms of cost‐effectiveness. © 2013 American Society for Bone and Mineral Research     

Adherence with bisphosphonate therapy and change in bone mineral density among women with osteoporosis or osteopenia in clinical practice

Summary

In clinical practice, adherence with bisphosphonate therapy varies greatly among women with osteoporosis or osteopenia. Our study suggests that better adherence with bisphosphonates confers tangible benefits in terms of graded increases in bone mineral density. Interventions to improve drug adherence should be an important component of disease management.

Introduction

In clinical trials, bisphosphonates have been found to increase bone mineral density (BMD) in women with osteoporosis or osteopenia. In clinical practice, where drug adherence is more variable, change in BMD with bisphosphonate therapy—overall and by level of adherence—is largely unknown.

Methods

A retrospective cohort study was conducted at Henry Ford Health System (Detroit, MI, USA). Study subjects were women who had low BMD at the left total hip (T-score?<??1.0), began oral bisphosphonate therapy, and had ≥1 BMD measurements at the left total hip ≥6 months following treatment initiation. Change in BMD was calculated between the most recent pretreatment scan and the first follow-up scan. Adherence (i.e., medication possession ratio (MPR)) was measured from therapy initiation to the first follow-up scan.

Results

Among 644 subjects, mean age was 66 years, pretreatment BMD was 0.73 g/cm², and pretreatment T-score was ?1.8. Over a mean follow-up of 27.1 months, mean MPR was 0.57 (95 % CI, 0.54 and 0.59), and mean percentage change in BMD was 1.5 % (1.1 and 1.9 %). Within the MPR strata (five consecutive equi-intervals, from low (0–0.19) to high (0.80–1.0)), mean change in BMD was ?0.8 % (?1.6 and 0.1 %), 0.7 % (?0.3 and 1.7 %), 2.1 % (1.1 and 3.0 %), 2.1 % (1.4 and 2.9 %), and 2.9 % (2.3 and 3.5 %), respectively. In adjusted analyses, percentage change in BMD was higher (by 1.4–3.4 %, p?<?0.05 for all) in the highest four MPR intervals, respectively, versus MPR 0–0.19.

Conclusions

Among women with osteoporosis or osteopenia in clinical practice, better adherence with bisphosphonates appears to confer tangible benefits in terms of increases in BMD.     

Use of Lowest Single Lumbar Spine Vertebra Bone Mineral Density T-Score and Other T-Score Approaches for Diagnosing Osteoporosis and Relationships with Vertebral Fracture Status

For diagnosing osteoporosis, International Society for Clinical Densitometry guidelines suggest using the lowest bone mineral density T-score of the lumbar spine (LS), femoral neck (FN), or total hip (TH). For the LS, use of the total spine (L1–L4) T-score is suggested. Although controversial, some authors have suggested using a single lumbar vertebra of L1–L4 with the lowest T-score to diagnose osteoporosis. We compared the ability of various T-score approaches [lowest single LS vertebra of L1–L4; total spine; FN; TH; and the lowest T-score of total spine, FN, or TH to diagnose osteoporosis in 2560 postmenopausal women from the Multiple Outcomes of Raloxifene Evaluation trial placebo group. The discriminatory ability of each T-score approach to identify women with or without vertebral fracture was compared using the area under receiver-operating characteristic curve. When the lowest single LS T-score of L1–L4 and the total spine T-score were used, 77% and 57% of women were categorized as having osteoporosis, respectively. These T-score approaches had similar ability for discriminating between women with or without prevalent vertebral fractures and for predicting the risk of incident vertebral fractures. The lowest single LS vertebra T-score identified a greater proportion of women with osteoporosis than currently accepted approaches. Thus, the WHO diagnostic classification should not be applied to single vertebral T-scores. This analysis supports the current International Society for Clinical Densitometry position to use the total spine T-score for osteoporosis diagnosis.     

Bone health management in patients with breast cancer: current standards and emerging strategies

In women who develop bone metastases from breast cancer (BC), interactions between tumor cells and osteoclasts within the bone lead to localized bone destruction and increase the risk of skeletal-related events (SREs). Bisphosphonates inhibit osteoclast-mediated bone resorption, and have been used extensively for treating post-menopausal osteoporosis and reducing the risk of SREs in patients with bone metastases. A number of clinical trials in women with early stage BC have demonstrated that adding bisphosphonates to adjuvant endocrine therapy can prevent bone loss and may prevent disease recurrence and improve disease-free survival. In women with bone metastases from BC, bisphosphonates have demonstrated efficacy for reducing skeletal morbidity and pain and improving quality of life. Recent economic analyses have demonstrated that bisphosphonate therapy is a cost-effective use of healthcare resources. This review summarizes the available data for bisphosphonate benefits in both the adjuvant and metastatic settings in the context of evolving clinical practice.     

Comparison of direct health care costs related to the pharmacological treatment of osteoporosis and to the management of osteoporotic fractures among compliant and noncompliant users of alendronate and risedronate: a population-based study

Summary  This population-based study aimed to compare direct health care costs related to the pharmacological treatment of osteoporosis and to the management of osteoporotic fractures among compliant and noncompliant users of alendronate and risedronate. During a 2-year follow-up period, compared to those with medication possession ratio (MPR) ≥ 80%, women with MPR < 80% incurred significantly higher physician care costs and hospital care costs. Introduction  This study aimed to compare direct health care costs related to the treatment of osteoporosis and osteoporotic fractures among compliant and noncompliant users of alendronate and risedronate. Methods  A cohort of 15,027 women having initiated alendronate or risedronate was identified. MPR and direct health care costs (physician care, hospital care, drugs) were assessed during a 2-year period. Regression models were used to estimate mean predicted cost for compliant (MPR ≥ 80%) and noncompliant (MPR < 80%) women. Results  Mean predicted physician care cost (in Canadian dollars) was $51 among women with MPR < 80% and $34 among those with MPR ≥ 80%: mean difference $17, 95% confidence interval (CI) $2–22. Mean predicted hospital care cost was $568 among women with MPR < 80% and $379 among those with MPR ≥ 80%: mean difference $189, 95% CI $56–320. Mean predicted drug cost was $439 among women with MPR < 80% and $1,068 among those with MPR ≥ 80%: mean difference $−639, 95% CI $−649 to −629. Conclusion  Compared to compliant women, noncompliant women incurred significantly higher physician care and hospital care costs. Due to lower drug costs, total direct health care costs were lower among noncompliant women.    This study was funded by a grant from the Canadian Institutes of Health Research (Ottawa, Canada)     

The prevalence of vertebral fracture amongst patients presenting with non-vertebral fractures

Introduction Despite vertebral fracture being a significant risk factor for further fracture, vertebral fractures are often unrecognised. A study was therefore conducted to determine the proportion of patients presenting with a non-vertebral fracture who also have an unrecognised vertebral fracture. Methods Prospective study of patients presenting with a non-vertebral fracture in South Glasgow who underwent DXA evaluation with vertebral morphometry (MXA) from DV5/6 to LV4/5. Vertebral deformities (consistent with fracture) were identified by direct visualisation using the Genant semi-quantitative grading scale. Results Data were available for 337 patients presenting with low trauma non-vertebral fracture; 261 were female. Of all patients, 10.4% were aged 50–64 years, 53.2% were aged 65–74 years and 36.2% were aged 75 years or over. According to WHO definitions, 35.0% of patients had normal lumbar spine BMD (T-score −1 or above), 37.4% were osteopenic (T-score −1.1 to −2.4) and 27.6% osteoporotic (T-score −2.5 or lower). Humerus (n=103, 31%), radius–ulna (n=90, 27%) and hand/foot (n=53, 16%) were the most common fractures. For 72% of patients (n=241) the presenting fracture was the first low trauma fracture to come to clinical attention. The overall prevalence of vertebral deformity established by MXA was 25% (n=83); 45% (n=37) of patients with vertebral deformity had deformities of more than one vertebra. Of the patients with vertebral deformity and readable scans for grading, 72.5% (58/80) had deformities of grade 2 or 3. Patients presenting with hip fracture, or spine T-score ≤−2.5, or low BMI, or with more than one prior non-vertebral fracture were all significantly more likely to have evidence of a prevalent vertebral deformity (p<0.05). However, 19.8% of patients with an osteopenic T-score had a vertebral deformity (48% of which were multiple), and 16.1% of patients with a normal T-score had a vertebral deformity (26.3% of which were multiple). Following non-vertebral fracture, some guidelines suggest that anti-resorptive therapy should be reserved for patients with DXA-proven osteoporosis. However, patients who have one or more prior vertebral fractures (prevalent at the time of their non-vertebral fracture) would also become candidates for anti-resorptive therapy—which would have not been the case had their vertebral fracture status not been known. Overall in this study, 8.9% of patients are likely to have had a change in management by virtue of their underlying vertebral deformity status. In other words, 11 patients who present with a non-vertebral fracture would need to undergo vertebral morphometry in order to identify one patient who ought to be managed differently. Conclusions Our results support the recommendation to perform vertebral morphometry in patients who are referred for DXA after experiencing a non-vertebral fracture. Treatment decisions will then better reflect any given patient’s future absolute fracture risk. The 'Number Needed to Screen' if vertebral morphometry is used in this way would be seven to identify one patient with vertebral deformity, and 14 to identify one patient with two or more vertebral deformities. Although carrying out MXA will increase radiation exposure for the patient, this increased exposure is significantly less than would be obtained if X-rays of the dorso-lumbar spine were obtained.     

Peripheral Quantitative Computed Tomography (pQCT) Measures Contribute to the Understanding of Bone Fragility in Older Patients With Low-trauma Fracture

Dual-energy X-ray absorptiometry (DXA) as currently used has limitations in identifying patients with osteoporosis and predicting occurrence of fracture. We aimed to express peripheral quantitative computed tomography (pQCT) variables of patients with low-trauma fracture as T-scores by using T-score scales obtained from healthy young women, and to evaluate the potential clinical utility of pQCT for the assessment of bone fragility. Fracture patients were recruited from a fracture liaison service at the Royal Melbourne Hospital. Reference pQCT data were obtained from studies on women's health conducted by our group. A study visit was arranged with fracture patients, during which DXA and pQCT were applied to measure their bone strength. A total of 59 fracture patients were recruited, and reference data were obtained from 78 healthy young females. All DXA variables and most pQCT variables were significantly different between healthy young females and fracture patients (p?<?0.05), except polar stress-strain index (p?=?0.34) and cortical bone density (p?=?0.19). Fracture patients were divided into osteoporosis and non-osteoporosis groups according to their DXA T-scores. Significant differences were observed in most pQCT variables (p?<?0.05), except trabecular area and cortical density (p?>?0.9 and p?=?0.5, respectively). By applying pQCT T-scores, 11 (27%) of patients who were classified as having low or medium risk of osteoporosis on DXA T-scores alone were reclassified as high risk. Results of logistic regression suggested trabecular bone density as an independent predictor of osteoporosis status. More patients can be identified with osteoporosis by applying pQCT T-score variables in older people with low-trauma fracture. Peripheral QCT T-scores contribute to the understanding of bone fragility in this population.     

Does scoliosis causes low bone mass? A comparative study between siblings

The aim of this study is to assess the prevalence low bone mass among girls with adolescent idiopathic scoliosis (AIS) and their siblings. The subjects of this study were Saudi Arabian girls with AIS. Patients had their weight and height measured to calculate their body mass index (BMI). Clinical examination and investigations were done to rule out any other cause of scoliosis. All had bone mineral density (BMD) measurement of hip area and the spine using DEXA scan, Hologic Inc. Patients with a BMD of < −2.6 was taken as osteoporotic and those between < −1 and −2.5 was taken as osteopenic for analysis. As control subjects, siblings of the patients with normal spine had their BMI calculated and BMD measurement done. We were able to analyze the data of 32 girls with an average age of 18.42 ± 5.71 (14–26) years with mean BMI of 17.7 ± 0.69 (16.5–18.5) kg/M². Analysis of the scans of the hip revealed that 62.5% of the patients were osteoporotic with BMD of 0.837 (0.697–0.936) ± 0.04, T-score −3.8 ± 0.56 (−2.6 to −3.9) and Z-score. Nine (28.1%) were osteopenic with BMD of 0.768 ± 0.15 (0.638–0.878), mean T-score of −1.6 (−1.1 to 2.5) and Z-score −3.5 ± 0.63 (−2.9 to −3.9). Analysis of BMD of the spine showed similar results. In comparison to the scoliotics, girls with normal spine had higher BMI and BMD which was statistically significant at P < 0.001. T- and Z-score was also lower in scoliotic girls in comparison with girls with normal spine significant at P < 0.001 (CI 95%). Our study indicates that the scoliosis causes osteopenia and osteoporosis among girls while their siblings with normal spine remain with normal bone mass.