Osteoporosis: Olszynski WP

Krieg MA, Barkmann R, Gonnelli S, Stewart A, Bauer DC, Del Rio Barquero L, Kaufman JJ, Lorenc R, Miller PD, Olszynski WP, Poiana C, Schott AM, Lewiecki EM, Hans D. · Lausanne University Hospital, Lausanne, Switzerland. <> · J Clin Densitom. · Pubmed #18442758 No free full text.

Abstract: Dual-energy X-ray absorptiometry (DXA) is commonly used in the care of patients for diagnostic classification of osteoporosis, low bone mass (osteopenia), or normal bone density; assessment of fracture risk; and monitoring changes in bone density over time. The development of other technologies for the evaluation of skeletal health has been associated with uncertainties regarding their applications in clinical practice. Quantitative ultrasound (QUS), a technology for measuring properties of bone at peripheral skeletal sites, is more portable and less expensive than DXA, without the use of ionizing radiation. The proliferation of QUS devices that are technologically diverse, measuring and reporting variable bone parameters in different ways, examining different skeletal sites, and having differing levels of validating data for association with DXA-measured bone density and fracture risk, has created many challenges in applying QUS for use in clinical practice. The International Society for Clinical Densitometry (ISCD) 2007 Position Development Conference (PDC) addressed clinical applications of QUS for fracture risk assessment, diagnosis of osteoporosis, treatment initiation, monitoring of treatment, and quality assurance/quality control. The ISCD Official Positions on QUS resulting from this PDC, the rationale for their establishment, and recommendations for further study are presented here.

Khan AA, Hanley DA, Bilezikian JP, Binkley N, Brown JP, Hodsman AB, Josse RG, Kendler DL, Lewiecki EM, Miller PD, Olszynski WP, Petak SM, Syed ZA, Theriault D, Watts NB, Anonymous00369. · Division of Endocrinology, McMaster University, Hamilton, Ontario, Canada, and Hanover General Hospital, PA, USA. · J Clin Densitom. · Pubmed #16731431 No free full text.

Abstract: This document addresses skeletal health assessment in individuals with secondary causes of osteoporosis. Recommendations are based on consensus of the Canadian Panel of the International Society for Clinical Densitometry and invited international experts. Bone mineral density (BMD) testing in these populations is performed in conjunction with careful evaluation of the disease state contributing to bone loss and increased fragility fracture risk, as well as assessment of other contributing risk factors for fracture. The presence of secondary causes of bone loss may further increase the risk of fracture independently of BMD and may necessitate earlier pharmacologic intervention. Dual-energy X-ray absorptiometry is indicated in the initial workup of secondary causes of osteoporosis. The BMD fracture risk relationship is not known for individuals with chronic renal failure (CRF). The BMD testing in this population may be normal in the presence of skeletal fragility, and quantitative bone histomorphometry is better at evaluating skeletal status than BMD in CRF. Dual-energy X-ray absorptiometry is a valuable tool in assessing skeletal health in individuals with secondary causes of osteoporosis.

Khan AA, Bachrach L, Brown JP, Hanley DA, Josse RG, Kendler DL, Leib ES, Lentle BC, Leslie WD, Lewiecki EM, Miller PD, Nicholson RL, O'Brien C, Olszynski WP, Theriault MY, Watts NB, Anonymous00235. · Divisions of Endocrinology and Geriatrics, McMaster University, Hamilton, ON, Canada. · J Clin Densitom. · Pubmed #14742888 No free full text.

Abstract: The Canadian Panel of the International Society for Clinical Densitometry has developed standards in order to establish the minimum level of acceptable performance for the practice of bone densitometry in Canada. Previously, this group addressed the performance of densitometry in postmenopausal women. This report addresses the use of densitometry in men, premenopausal women, and children with a focus on dual-energy X-ray absorptiometry.

Khan AA, Brown J, Faulkner K, Kendler D, Lentle B, Leslie W, Miller PD, Nicholson L, Olszynski WP, Watts NB, Anonymous00159. · McMaster University, Oakville, Ontario, Canada. · J Clin Densitom. · Pubmed #12665644 No free full text.

Abstract: The International Society for Clinical Densitometry (ISCD) is a multidisciplinary nonprofit global organization formed to ensure excellence in densitometry imaging, interpretation, and application. The Canadian panel of the ISCD represents ISCD in Canada and oversees Canadian bone densitometry certification programs. The standards of care from the Canadian panel of the ISCD have been developed in order to establish the minimum level of acceptable performance for the practice of bone densitometry in Canada. A variety of techniques are available for skeletal assessment of bone mineral density, which vary in accuracy, precision, and clinical utility as well as availability. This article focuses on central dual X-ray absorptiometry in adults and does not address densitometry in the pediatric population. Other technologies will be addressed in a subsequent article.

Olszynski WP, Davison KS. · University of Saskatchewan, Saskatoon, SK, Canada. · Expert Opin Pharmacother. · Pubmed #18220499 No free full text.

Abstract: BACKGROUND: Men have higher rates of osteoporosis and suffer fragility fractures more often than previously believed. Fracture-related morbidity and mortality in men is substantially higher than in women. OBJECTIVE: To investigate alendronate for treating osteoporosis in men. METHODS: Search limited to 'men' and 'English'; keywords were 'osteoporosis' or 'bone density' or 'fracture' and 'alendronate'. RESULTS/CONCLUSIONS: Alendronate is an amino-bisphosphonate with proved efficacy for increasing bone mineral density in men with idiopathic or secondary osteoporosis and has demonstrated an ability to prevent vertebral fractures in men with low bone mass. There are trends for alendronate to decrease the risk of non-vertebral fracture, but larger trials are needed to conclusively establish this benefit. Alendronate is a well-tolerated and comparatively safe drug with an attractive once-a-week dosing regimen.

Khan AA, Hodsman AB, Papaioannou A, Kendler D, Brown JP, Olszynski WP. · Division of Endocrinology and Geriatrics, Department of Medicine, McMaster University, Hamilton, Ont. · CMAJ. · Pubmed #17261833 links to  free full text

Abstract: In 2002, Osteoporosis Canada published clinical practice guidelines for the diagnosis and management of osteoporosis. The current paper supplements that guideline and provides a review and synthesis of the current literature on the diagnosis and management of osteoporosis in men.

Hodsman AB, Bauer DC, Dempster DW, Dian L, Hanley DA, Harris ST, Kendler DL, McClung MR, Miller PD, Olszynski WP, Orwoll E, Yuen CK. · University of Western Ontario, St. Joseph's Health Care, Room 2F-15, 268, Grosvenor Street, London, Ontario N6A 4V2, Canada. · Endocr Rev. · Pubmed #15769903 links to  free full text

Abstract: All therapies currently recommended for the management of osteoporosis act mainly to inhibit bone resorption and reduce bone remodeling. PTH and its analog, teriparatide [recombinant human PTH(1-34)], represent a new class of anabolic therapies for the treatment of severe osteoporosis, having the potential to improve skeletal microarchitecture. Significant reductions in both vertebral and appendicular fracture rates have been demonstrated in the phase III trial of teriparatide, involving elderly women with at least one prevalent vertebral fracture before the onset of therapy. However, there is as yet no evidence that the antifracture efficacy of PTH will be superior to the bisphosphonates, whereas cost-utility estimates suggest that teriparatide is significantly more expensive. Teriparatide should be considered as treatment for postmenopausal women and men with severe osteoporosis, as well as for patients with established glucocorticoid-induced osteoporosis who require long-term steroid treatment. Teriparatide should also be considered for the management of individuals at particularly high risk for fractures, including subjects who are younger than age 65 and who have particularly low bone mineral density measurements (T scores < or = 3.5). Teriparatide therapy is not recommended for more than 2 yr, based, in part, on the induction of osteosarcoma in a rat model of carcinogenicity. Total daily calcium intake from both supplements and dietary sources should be limited to 1500 mg together with adequate vitamin D intake (< or =1000 U/d). Monitoring of serum calcium may be safely limited to measurement after 1 month of treatment; mild hypercalcemia may be treated by withdrawing dietary calcium supplements, reducing the dosing frequency of PTH, or both. At present, concurrent therapy with antiresorptive therapy, particularly bisphosphonates, should be avoided, although sequential therapy with such agents may consolidate the beneficial effects upon the skeleton after PTH is discontinued.

Olszynski WP, Shawn Davison K, Adachi JD, Brown JP, Cummings SR, Hanley DA, Harris SP, Hodsman AB, Kendler D, McClung MR, Miller PD, Yuen CK. · Department of Medicine, University of Saskatchewan, Saskatoon Osteoporosis Centre, Saskatoon, Saskatchewan, Canada. · Clin Ther. · Pubmed #14996514 No free full text.

Abstract: BACKGROUND: Osteoporosis and fragility fractures in men account for substantial health care expenditures and decreased quality of life. OBJECTIVE: This article reviews the most current information about the epidemiology, diagnosis, prevention, and treatment of osteoporosis in men. METHODS: Relevant literature was identified through a search of MEDLINE (1966-June 2003) limited to English-language studies in men. The search terms included fractures, bone density, or osteoporosis plus either epidemiology, diagnosis, prevention, control, or therapy. Additional search terms included specific subtopics (eg, bisphosphonates, calcium, exercise, parathyroid hormone). The authors contributed additional relevant publications. RESULTS: Morbidity after fragility fracture is at least as high in men as in women, and the rate of fracture-related mortality 1 year hip fracture is approximately double in men compared with women. The bioavailable fraction of testosterone slowly declines into the ninth decade in men. There is evidence that the effect of estrogen on bone is greater than that of testosterone in men. Diagnosing osteoporosis in men is complicated by a lack of consensus on how it should be defined. Significant risk factors for osteoporosis or fracture include low bone mineral density, previous fragility fracture, maternal history of fracture, marked hypogonadism, smoking, heavy alcohol intake or alcoholism, low calcium intake, low body mass or body mass index, low physical activity, use of bone-resorbing medication such as glucocorticoids, and the presence of such conditions as hyperthyroidism, hyperparathyroidism, and hypercalciuria. Prevention is paramount and should begin in childhood. During adulthood, calcium (1000-1500 mg/d), vitamin D (400-800 IU/d), and adequate physical activity play crucial preventive roles. When treatment is indicated, the bisphosphonates are the first choice, whereas there is less support for the use of calcitonin or androgen therapy. Parathyroid hormone (1-34) is a promising anabolic therapy. There is also strong evidence for the use of bisphosphonates for the treatment of glucocorticoid-induced osteoporosis.

Adachi JD, Olszynski WP, Hanley DA, Hodsman AB, Kendler DL, Siminoski KG, Brown J, Cowden EA, Goltzman D, Ioannidis G, Josse RG, Ste-Marie LG, Tenenhouse AM, Davison KS, Blocka KL, Pollock AP, Sibley J. · Department of Medicine, St Joseph's Hospital, McMaster University, Hamilton, Ontario, Canada. · Semin Arthritis Rheum. · Pubmed #10707991 No free full text.

Abstract: OBJECTIVES: To educate scientists and health care providers about the effects of corticosteroids on bone, and advise clinicians of the appropriate treatments for patients receiving corticosteroids. METHODS: This review summarizes the pathophysiology of corticosteroid-induced osteoporosis, describes the assessment methods used to evaluate this condition, examines the results of clinical trials of drugs, and explores a practical approach to the management of corticosteroid-induced osteoporosis based on data collected from published articles. RESULTS: Despite our lack of understanding about the biological mechanisms leading to corticosteroid-induced bone loss, effective therapy has been developed. Bisphosphonate therapy is beneficial in both the prevention and treatment of corticosteroid-induced osteoporosis. The data for the bisphosphonates are more compelling than for any other agent. For patients who have been treated but continue to lose bone, hormone replacement therapy, calcitonin, fluoride, or anabolic hormones should be considered. Calcium should be used only as an adjunctive therapy in the treatment or prevention of corticosteroid-induced bone loss and should be administered in combination with other agents. Conclusions: Bisphosphonates have shown significant treatment benefit and are the agents of choice for both the treatment and prevention of corticosteroid-induced osteoporosis.

Delmas PD, Benhamou CL, Man Z, Tlustochowicz W, Matzkin E, Eusebio R, Zanchetta J, Olszynski WP, Recker RR, McClung MR. · University of Lyon and INSERM Research Unit 831, Lyon, France. · Osteoporos Int. · Pubmed #18087660 No free full text.

Abstract: SUMMARY: Postmenopausal women with osteoporosis received 75 mg risedronate on two consecutive days each month or 5 mg daily for 12 months. Changes in bone mineral density and bone turnover markers were similar between treatments. Risedronate 75 mg twice monthly was effective and safe suggesting a new, convenient dosing schedule. INTRODUCTION: Patients perceive less frequent dosing as being more convenient. This 2-year trial evaluates the efficacy and safety of a new monthly oral regimen of risedronate; 1 year results are presented here. METHODS: Postmenopausal women with osteoporosis (n = 1229) were randomly assigned to double-blind treatment with 75 mg risedronate on two consecutive days each month (2CDM), or 5 mg daily. The primary endpoint was the percent change from baseline in lumbar spine (LS) bone mineral density (BMD) at month 12. Secondary efficacy was evaluated by mean percent changes from baseline in BMD in LS, total hip, trochanter, and femoral neck, and bone turnover markers (BTMs). RESULTS: Risedronate 75 mg 2CDM was non-inferior to 5 mg daily (treatment difference 0.21; 95% CI -0.19 to 0.62). Mean percent change in LS-BMD was 3.4% +/- 0.16 and 3.6% +/- 0.15 respectively. Mean percent changes in BMD and BTMs were significant and similar for both treatment groups. New vertebral fractures occurred in 1% of subjects with either treatment. Both treatments were generally well tolerated and safe. CONCLUSIONS: Risedronate 75 mg 2CDM was non-inferior in efficacy and did not show a difference in safety vs. 5 mg daily after 12 months, leading to a similar benefit.

Heaney RP, Zizic TM, Fogelman I, Olszynski WP, Geusens P, Kasibhatla C, Alsayed N, Isaia G, Davie MW, Chesnut CH. · Creighton University, Omaha, Nebraska 68131, USA. · Osteoporos Int. · Pubmed #12107665 No free full text.

Abstract: Risedronate treatment reduces the risk of vertebral fracture in women with existing vertebral fractures, but its efficacy in prevention of the first vertebral fracture in women with osteoporosis but without vertebral fractures has not been determined. We examined the risk of first vertebral fracture in postmenopausal women who were enrolled in four placebo-controlled clinical trials of risedronate and who had low lumbar spine bone mineral density (BMD) (mean T-score = -3.3) and no vertebral fractures at baseline. Subjects received risedronate 5 mg ( n = 328) or placebo ( n = 312) daily for up to 3 years; all subjects were given calcium (1000 mg daily), as well as vitamin D supplementation (up to 500 IU daily) if baseline serum 25-hydroxyvitamin D levels were low. The incidence of first vertebral fracture was 9.4% in the women treated with placebo and 2.6% in those treated with risedronate 5 mg (risk reduction of 75%, 95% confidence interval 37% to 90%; P = 0.002). The number of patients who would need to be treated to prevent one new vertebral fracture is 15. When subjects were stratified by age, similar significant reductions were observed in patients with a mean age of 64 years (risk reduction of 70%, 95% CI 8% to 90%; P = 0.030) and in those with a mean age of 76 years (risk reduction of 80%, 95% CI 7% to 96%; P = 0.024). Risedronate treatment therefore significantly reduces the risk of first vertebral fracture in postmenopausal women with osteoporosis, with a similar magnitude of effect early and late after the menopause.

Adachi JD, Adami S, Miller PD, Olszynski WP, Kendler DL, Silverman SL, Licata AA, Li Z, Gomez-Panzani E. · Department of Medicine, St. Joseph's Hospital, McMaster University, Hamilton, Ontario, Canada, · Aging (Milano). · Pubmed #11820707 No free full text.

Abstract: Bisphosphonates are effective treatments for osteoporosis, but some have been associated with upper gastrointestinal intolerance. This randomized, double-blind study assessed the upper gastrointestinal tolerability of risedronate in postmenopausal women who had discontinued alendronate treatment because of upper gastrointestinal adverse events. Sixty-six women who had previously discontinued treatment with alendronate 10 mg/day because of upper gastrointestinal symptoms received placebo (N=31) or risedronate 5 mg (N=35) daily for 3 months. The primary outcome was the rate of discontinuation due to upper gastrointestinal adverse events: 5/31 (16.1%) in the placebo group, and 4/35 (11.4%) in the risedronate group. Discontinuation rates were also similar in the two treatment groups among subgroups of patients with a history of gastrointestinal disorder, prior use of acid suppression drugs, and concomitant use of NSAIDs. The overall incidence of upper gastrointestinal events was comparable between the placebo (19.4%) and risedronate (20.0%) groups. Overall, risedronate 5 mg/day for 3 months was as well tolerated as placebo in patients who could not tolerate alendronate 10 mg. These results are consistent with, and complement those from previous studies showing that risedronate 5 mg has a gastrointestinal tolerability similar to that of placebo.

Brown JP, Olszynski WP, Hodsman A, Bensen WG, Tenenhouse A, Anastassiades TP, Ste-Marie LG, Kendler DL, Hanley DA, Josse R, Hanly JG, Lentle B, Jovaisas A, Ioannidis G, Stephenson GF, Barton I, Pack S, Chines A, Dias R, Adachi JD. · Centre de Recherche du CHUL, Centre Hospitalier Universitaire de Quebec, 2705 boul Laurier #S-784, Ste-Foy, Québec, G1V 4G2 Canada. · J Clin Densitom. · Pubmed #11748341 No free full text.

Abstract: Following a 52-wk randomized controlled trial of intermittent cyclic etidronate therapy in patients using corticosteroids, we performed a 52-wk open-label trial of calcium alone in 114 corticosteroid-treated patients to determine whether the beneficial effect of etidronate is maintained after the drug is discontinued. All patients were given 500 mg/d of elemental calcium. Sixty-one and 53 patients made up the former placebo and etidronate groups, respectively. A total of 89 (98%) of patients in the former placebo and etidronate groups remained on corticosteroids throughout the second year. The mean (SE) percentage change in bone mineral density of the lumbar spine, femoral neck, and trochanter were compared between groups. The difference between groups in mean percentage change from baseline (wk 0, initiation of etidronate or placebo therapy) in the bone density of the lumbar spine, femoral neck, and trochanter, following 104 wk, was 3.8 (0.9), 3.0 (1.1), and 4.3 (1.1), respectively (p < 0.05, all sites), in favor of the former etidronate group. While not significant, the former placebo group demonstrated a slightly larger rate of decline in bone density over the second year than the former etidronate group at all three sites. Following the discontinuation of etidronate therapy, there was no accelerated bone loss and there was evidence of a residual protective effect in both the lumbar spine and femoral neck for up to 1 yr posttreatment.

Chen P, Krege JH, Adachi JD, Prior JC, Tenenhouse A, Brown JP, Papadimitropoulos E, Kreiger N, Olszynski WP, Josse RG, Goltzman D, Anonymous00060. · Eli Lilly and Company, Indianapolis, Indiana, USA. · J Bone Miner Res. · Pubmed #19016585 No free full text.

Abstract: Vertebral fractures are the most common osteoporotic fracture, and patients with prevalent vertebral fractures have a greater risk of future fractures. However, radiographically determined vertebral fractures are not identified as a distinct risk factor in the World Health Organization (WHO) fracture risk assessment tool. The objective of this study was to evaluate and compare potential risk factors including morphometric spine fracture status and the WHO risk factors for predicting 5-yr fracture risk. We hypothesized that spine fracture status provides prognostic information in addition to consideration of the WHO risk factors alone. A randomly selected, population-based community cohort of 2761 noninstitutionalized men and women > or =50 yr of age living within 50 km of one of nine regional centers was enrolled in the Canadian Multicentre Osteoporosis Study (CaMOS), a prospective and longitudinal cohort study following subjects for 5 yr. Prevalent and incident spine fractures were identified from lateral spine radiographs. Incident nonvertebral fragility fractures were determined by an annual, mailed fracture questionnaire with validation, and nonvertebral fragility fracture was defined by investigators as a fracture with minimal trauma. A model considering the WHO risk factors plus spine fracture status provided greater prognostic information regarding future fracture risk than a model considering the WHO risk factors alone. In univariate analyses, age, BMD, and spine fracture status had the highest gradient of risk. A model considering these three risk factors captured almost all of the predictive information provided by a model considering spine fracture status plus the WHO risk factors and provided greater predictive information than a model considering the WHO risk factors alone. The use of spine fracture status along with age and BMD predicted future fracture risk with greater simplicity and higher prognostic accuracy than consideration of the risk factors included in the WHO tool.

Papaioannou A, Kennedy CC, Ioannidis G, Sawka A, Hopman WM, Pickard L, Brown JP, Josse RG, Kaiser S, Anastassiades T, Goltzman D, Papadimitropoulos M, Tenenhouse A, Prior JC, Olszynski WP, Adachi JD, Anonymous00108. · McMaster University, Hamilton Health Sciences-Chedoke Site, Hamilton, ON, Canada. · Osteoporos Int. · Pubmed #18802659 No free full text.

Abstract: Using prospective data from the Canadian Multicentre Osteoporosis Study (CaMos), we compared health utilities index (HUI) scores after 5 years of follow-up among participants (50 years and older) with and without incident clinical fractures. Incident fractures had a negative impact on HUI scores over time. INTRODUCTION: This study examined change in health-related quality of life (HRQL) in those with and without incident clinical fractures as measured by the HUI. METHODS: The study cohort was 4,820 women and 1,783 men (50 years and older) from the CaMos. The HUI was administered at baseline and year 5. Participants were sub-divided into incident fracture groups (hip, rib, spine, forearm, pelvis, other) and were compared with those without these fractures. The effects of both time and fracture type on HUI scores were examined in multivariable regression analyses. RESULTS: Men and women with hip fractures, compared to those without, had lower HUI measures that ranged from -0.05 to -0.25. Both women and men with spine fractures had significant deficits on the pain attributes (-0.07 to -0.12). In women, self-care (-0.06), mobility and ambulation (-0.05) were also negatively impacted. Women with rib fractures had deficits similar to women with spine fractures, and these effects persisted over time. In men, rib fractures did not significantly affect HUI scores. Pelvic and forearm fractures did not substantially influence HUI scores. CONCLUSION: The HUI was a sensitive measure of HRQL change over time. These results will inform economic analyses evaluating osteoporosis therapies.

Langsetmo LA, Morin S, Richards JB, Davison KS, Olszynski WP, Prior JC, Josse R, Goltzman D, Anonymous00090. · CaMos National Coordinating Centre, Montreal, Canada. · Osteoporos Int. · Pubmed #18581034 No free full text.

Abstract: SUMMARY: Observational studies are needed to quantify real-life effectiveness of antiresorptive therapy in the prevention of clinical fractures. Antiresorptive therapies were associated with an overall 32% reduction in low-trauma nonvertebral fracture risk among women 50 and older. Effectiveness may be lower among older women and those without risk factors. INTRODUCTION: Randomized controlled trials have shown that antiresorptive therapies reduce the risk of fracture in selected populations, but further study is needed to quantify their real-life effectiveness. The study objective was to determine the association between antiresorptive use and low-trauma nonvertebral fracture in women 50 and older. METHODS: The design was a retrospective nested case-control study (density-based sampling) within the Canadian Multicentre Osteoporosis Study. There were 5,979 eligible women with 453 cases and 1,304 matched controls. RESULTS: The current use of antiresorptives was associated with a decreased risk of fracture with OR = 0.68, 95% CI: 0.52-0.91; where OR is the adjusted odds ratio and CI is the confidence interval. Subgroup analysis yielded OR = 0.61, 95% CI: 0.42-0.89 for ages 50-74; OR = 0.76, 95% CI: 0.50-1.17 for ages 75+; OR = 0.58, 95% CI: 0.40-0.83 for those with a major risk factor; and OR = 0.92; 95% CI: 0.59-1.42 for those without a major risk factor. Major risk factors were prevalent low-trauma fracture, vertebral deformity (grade 2+), and BMD T-score < or = -2.5. CONCLUSIONS: Antiresorptive therapy is associated with a clinically important reduction in low-trauma nonvertebral fracture risk among community-dwelling women aged 50 and older. Antiresorptive therapy may be less effective for women 75 and older and women without major risk factors.

Watts NB, Chines A, Olszynski WP, McKeever CD, McClung MR, Zhou X, Grauer A. · University of Cincinnati Bone Health and Osteoporosis Center, 222 Piedmont Avenue, Suite 4300, Cincinnati, OH 45219, USA. · Osteoporos Int. · Pubmed #17938986 No free full text.

Abstract: SUMMARY: One year after discontinuation of three year's treatment with risedronate, BMD decreased at the lumbar spine and femoral neck and bone turnover markers returned to control group levels. Despite these changes, the risk of new morphometric vertebral fractures remained lower in previous risedronate patients compared with previous control patients. INTRODUCTION: Differences in bisphosphonate pharmacology and pharmacokinetics could influence persistence or resolution of the effects once treatment is stopped. We investigated changes in intermediate markers--bone mineral density (BMD) and bone turnover markers (BTM)--and fracture risk after discontinuation of treatment with risedronate. METHODS: Patients who received risedronate 5 mg daily (N = 398) or placebo (N = 361) during the VERT-NA study stopped therapy per protocol after 3 years but continued taking vitamin D (if levels at study entry were low) and calcium and were reassessed one year later. RESULTS: In the year off treatment, spine BMD decreased significantly, but remained higher than baseline (p < or = 0.001) and placebo (p < 0.001), with similar findings at the femoral neck and trochanter. Urinary NTX and bone-specific alkaline phosphatase, which decreased significantly with treatment, were not significantly different from placebo after 1 year off treatment. Despite the changes in intermediate markers, the incidence of new morphometric vertebral fractures was 46% lower in the former risedronate group compared with the former placebo group (RR 0.54 [95% CI, 0.34, 0.86, p = 0.009]). CONCLUSIONS: Despite the apparent resolution of effect on BMD and BTM, the risk reduction of new vertebral fractures remained in the year after treatment with risedronate was stopped.

Papaioannou A, Kennedy CC, Ioannidis G, Gao Y, Sawka AM, Goltzman D, Tenenhouse A, Pickard L, Olszynski WP, Davison KS, Kaiser S, Josse RG, Kreiger N, Hanley DA, Prior JC, Brown JP, Anastassiades T, Adachi JD, Anonymous00061. · Division of Geriatric Medicine, McMaster University, Hamilton Health Sciences-Chedoke Site, 1200 Main Street West, Hamilton, ON L8N 3Z5, Canada. · Osteoporos Int. · Pubmed #17924051 No free full text.

Abstract: SUMMARY: We examined osteoporosis diagnosis/treatment in 2,187 community dwelling men age 50+. After five years in the study, 90% of men with fragility fractures remained undiagnosed and untreated for osteoporosis. The need to treat fragility fractures is well established in guidelines, and these numbers represent an important care gap. INTRODUCTION: Whether physicians in the community are recognizing and appropriately treating osteoporosis and fragility fractures in men remains unknown. We examined the rate of diagnosis and treatment in community dwelling men participating in the Canadian Multicentre Osteoporosis Study (CaMos). METHODS: Between February 1996 and September 2002, 2,187 participants were recruited from nine sites across Canada and prospectively followed. Information on osteoporosis diagnosis, fractures, medications were collected annually by a detailed questionnaire. DXA examination of lumbar spine (L1-4) and hip were conducted at baseline and year five. RESULTS: Diagnosis and treatment in men with clinical fragility fractures was low: at baseline and year five only 2.3% and 10.3% of men with a clinical fracture reported an osteoporosis diagnosis, respectively. At year five, 90% of men with a clinical fragility fracture were untreated. Hip fractures were the most commonly treated (37.5% by year five). A diagnosis of osteoporosis resulted in greater treatment: 67% of participants with diagnosed osteoporosis were treated with a bisphosphonate and 87% were taking calcium and/or vitamin D (year five). CONCLUSIONS: In this population-based study, both a diagnostic and therapeutic gap existed between knowledge and practice related to fragility fractures and osteoporosis in men aged >or=50 years.

Papaioannou A, Kennedy CC, Ioannidis G, Brown JP, Pathak A, Hanley DA, Josse RG, Sebaldt RJ, Olszynski WP, Tenenhouse A, Murray TM, Petrie A, Goldsmith CH, Adachi JD. · Department of Medicine, McMaster University, Hamilton, Ontario, Canada. · Osteoporos Int. · Pubmed #16341623 No free full text.

Abstract: Health-related quality of life (HRQL) is an important consideration in the management of patients with vertebral fractures. The purpose of this study was to examine patient-related factors that contribute to HRQL after vertebral fractures, including co-morbidities, medications, fracture history, family disease history, demographics, exercise, education and living environment. A total of 1,129 post-menopausal women (mean age 67.2, SD 11.9 years) was studied from the Canadian Database of Osteoporosis and Osteopenia (CANDOO). HRQL was measured using the mini-osteoporosis quality of life questionnaire (mini-OQLQ). Separate multivariable linear regression analyses [parameter estimates and corresponding 95% confidence intervals (CI)] were performed for each of the five mini-OQLQ domains: symptoms, physical functioning, emotional functioning, activities of daily living and leisure domains. A strong positive association was found between HRQL and post-secondary education, a family history of osteoporosis, working and thiazide therapy. Exercise improved HRQL; however, several hours a week were required to be meaningful. Living in long-term care had the most marked negative effect on HRQL. Smoking, past surgery of the hip or spine, sedatives, anticonvulsants, atherosclerotic disease and hypertension were also associated with a substantially decreased HRQL across several domains. Calcium channel-blockers, chemotherapy, corticosteroids, diabetes, migraines, the number of non-vertebral fractures and falls had a negative impact on selected domains. We demonstrated that several modifiable factors influence HRQL in patients with vertebral fractures, and physicians should be aware of these and other markers of reduced HRQL to enhance patient care.

Sawka AM, Ioannidis G, Papaioannou A, Thabane L, Olszynski WP, Brown JP, Hanley DA, Murray TM, Josse RG, Sebaldt RJ, Petrie A, Tenenhouse A, Goldsmith CH, Boulos P, Kouroukis T, Adachi JD. · Department of Medicine, St. Joseph's Healthcare and McMaster University, Hamilton ON. · J Obstet Gynaecol Can. · Pubmed #16287007 No free full text.

Abstract: OBJECTIVE: Breast cancer survivors with osteoporosis or osteopenia are commonly encountered in primary care and gynaecology practices. Our objective was to determine whether treatment with oral bisphosphonates (alendronate or cyclic etidronate) was more effective than calcium with vitamin D in improving lumbar spine bone mineral density (BMD) within one year in breast cancer survivors. METHODS: Breast cancer survivors with at least one year of clinical follow-up were identified from the prospective observational Canadian Database of Osteoporosis and Osteopenia (CANDOO). Analysis of covariance was used to examine the effects of bisphosphonate therapy on change in lumbar spine BMD at one year compared with the effects of calcium with vitamin D (analysis adjusted for baseline L2-L4 BMD, current tamoxifen use, number of prevalent vertebral fractures [VFs], and time since diagnosis of breast cancer, and age). RESULTS: Eighteen patients took calcium and vitamin D, 25 took cyclic etidronate, and 27 took oral alendronate. Adjusted one-year BMD increases for alendronate and cyclic etidronate compared to calcium and vitamin D were as follows: alendronate 4.53% (95% confidence interval [CI] 1.26%, 7.81%, P = 0.008), and cyclic etidronate 1.85% (-1.55%, 5.25%, P = 0.280). BMD increases were significantly greater in patients with prevalent VF compared to those without VF (P = 0.025). In contrast, time since diagnosis of breast cancer was significantly associated with a decrease in BMD (P = 0.002). We were unable to detect any effect of current tamoxifen use, baseline lumbar spine BMD, or age on changes in BMD at one year. CONCLUSION: Treatment with alendronate was associated with significantly greater improvements in lumbar spine BMD within one year in breast cancer survivors when compared with treatment with cyclic etidronate or calcium and vitamin D.

Bensen R, Adachi JD, Papaioannou A, Ioannidis G, Olszynski WP, Sebaldt RJ, Murray TM, Josse RG, Brown JP, Hanley DA, Petrie A, Puglia M, Goldsmith CH, Bensen W. · Medical Science, McMaster University, Hamilton, Ontario, Canada. · BMC Musculoskelet Disord. · Pubmed #16143046 links to  free full text

Abstract: BACKGROUND: Fracture represents the single most important clinical event in patients with osteoporosis, yet remains under-predicted. As few premonitory symptoms for fracture exist, it is of critical importance that physicians effectively and efficiently identify individuals at increased fracture risk. METHODS: Of 3426 postmenopausal women in CANDOO, 40, 158, 99, and 64 women developed a new hip, vertebral, wrist or rib fracture, respectively. Seven easily measured risk factors predictive of fracture in research trials were examined in clinical practice including: age (< 65, 65-69, 70-74, 75-79, 80+ years), rising from a chair with arms (yes, no), weight (< 57, > or = 57 kg), maternal history of hip fracture (yes, no), prior fracture after age 50 (yes, no), hip T-score (> -1, -1 to > -2.5, < or = -2.5), and current smoking status (yes, no). Multivariable logistic regression analysis was conducted. RESULTS: The inability to rise from a chair without the use of arms (3.58; 95% CI: 1.17, 10.93) was the most significant risk factor for new hip fracture. Notable risk factors for predicting new vertebral fractures were: low body weight (1.57; 95% CI: 1.04, 2.37), current smoking (1.95; 95% CI: 1.20, 3.18) and age between 75-79 years (1.96; 95% CI: 1.10, 3.51). New wrist fractures were significantly identified by low body weight (1.71, 95% CI: 1.01, 2.90) and prior fracture after 50 years (1.96; 95% CI: 1.19, 3.22). Predictors of new rib fractures include a maternal history of a hip fracture (2.89; 95% CI: 1.04, 8.08) and a prior fracture after 50 years (2.16; 95% CI: 1.20, 3.87). CONCLUSION: This study has shown that there exists a variety of predictors of future fracture, besides BMD, that can be easily assessed by a physician. The significance of each variable depends on the site of incident fracture. Of greatest interest is that an inability to rise from a chair is perhaps the most readily identifiable significant risk factor for hip fracture and can be easily incorporated into routine clinical practice.

Olszynski WP, Davison KS, Ioannidis G, Brown JP, Hanley DA, Josse RG, Murray TM, Papaioannou A, Sebaldt RJ, Tenenhouse AM, Petrie A, Goldsmith CH, Adachi JD. · Saskatoon Osteoporosis Centre, Saskatoon, SK, S7K 0H6, Canada. · Osteoporos Int. · Pubmed #15997420 No free full text.

Abstract: The prevalence of osteoporosis in men is higher than previously assumed; consequently, numerous therapies are being investigated to treat these patients. The Canadian Database of Osteoporosis and Osteopenia patients (CANDOO) was analyzed to examine changes in bone mineral density (BMD) in consecutively seen osteoporotic men administered alendronate, etidronate or no bone-active drugs (control) over 1 year. A total of 244 men attending six Canadian osteoporosis clinics were included in the study (42 alendronate, 102 etidronate and 100 control). Multiple imputation was used to model missing data to provide a more robust statistical model. The imputed datasets (five) were analyzed using multivariable linear regression to determine differences between groups in the percent change of lumbar spine (LS) and femoral neck (FN) BMD from baseline to 1 year. Differences in the percent change in BMD from baseline were most notable at the LS in favor of alendronate (4.3%; 95% CI: 2.1, 6.6 ) and etidronate (2.1%; 95% CI: 0.3, 4.0) therapy when compared with controls. At the LS, alendronate therapy led to significantly greater (2.2%; 95% CI: 0.2, 4.2) gains in BMD as compared to etidronate therapy. Compared to controls, there were no significant differences in FN BMD with alendronate (2.1%; 95% CI: -0.4, 4.7) or etidronate therapy (0.9%; 95% CI: -1.1, 2.8), nor were there significant differences between bisphosphonate groups (1.3%; 95% CI: -1.1, 3.6, in favor of alendronate). While both alendronate and etidronate significantly increased LS BMD in osteoporotic men after 1 year in real-world settings, alendronate therapy resulted in significantly superior gains in LS BMD. The effect of these two bisphosphonates on fractures and FN BMD in osteoporotic men is likely positive, but requires further study.

Papaioannou A, Joseph L, Ioannidis G, Berger C, Anastassiades T, Brown JP, Hanley DA, Hopman W, Josse RG, Kirkland S, Murray TM, Olszynski WP, Pickard L, Prior JC, Siminoski K, Adachi JD. · Department of Medicine, St. Joseph's Hospital, McMaster University, Hamilton, Ontario, Canada. · Osteoporos Int. · Pubmed #15517191 No free full text.

Abstract: Utilizing data from the Canadian Multicentre Osteoporosis Study (CaMos), we examined the association between potential risk factors and incident vertebral and nonvertebral fractures. A total of 5,143 postmenopausal women were enrolled. Information collected during the study included data from the CaMos baseline and annually mailed fracture questionnaires, the Short Form 36 (SF-36), the Health Utilities Index, and physical measurements. Participants were followed for 3 years. Postmenopausal women were classified into four groups according to their incident fracture status since baseline: those without a new fracture; those with a new clinically recognized vertebral fracture; those with an incident nonvertebral fracture at the wrist, hip, humerus, pelvis, or ribs (main nonvertebral fracture group); and those with any new nonvertebral fracture (any-nonvertebral-fracture group). We performed multivariate Cox proportional hazard analysis using all possible risk factors to determine the association between risk factors and the time to the first minimal trauma fracture. Best predictive models were also determined using variables that were included in the full models. The Bayesian information criterion was used for model selection. For all analyses, relative risks and associated 95% confidence intervals were calculated. During the follow-up period, 34, 163, and 280 women developed a vertebral, a main nonvertebral, or any nonvertebral fracture, respectively. The best predictive models indicated that a five point lower quality of life as measured by the SF-36 physical component summary score was associated with relative risks of 1.21 (95% CI, 1.02 to 1.44), 1.17 (95% CI, 1.07 to 1.28), and 1.19 (95% CI, 1.11 to 1.27) for incident vertebral, main nonvertebral, and all nonvertebral fractures, respectively. In addition, for a one standard deviation (SD=0.12) lower femoral neck BMD, the relative risks for incident vertebral, main nonvertebral, and any nonvertebral fractures increased by 2.73 (95% CI, 1.74 to 4.28), 1.39 (95% CI, 1.06 to 1.82), and 1.34 (95% CI, 1.09 to 1.65), respectively. Furthermore, various anthropometric measures, disease conditions, and medications are associated with a new fracture. Identifying postmenopausal women at risk is important given that fracture prevention therapies are now available.

Sawka AM, Adachi JD, Papaioannou A, Thabane L, Ioannidis G, Davison KS, Olszynski WP, Brown JP, Hanley DA, Murray TM, Josse RG, Sebaldt RJ, Petrie A, Tenenhouse A, Goldsmith CH. · McMaster University, St. Joseph's Healthcare, Centre for Evaluation of Medicines, Hamilton, Ontario, Canada. · J Rheumatol. · Pubmed #15468365 No free full text.

Abstract: OBJECTIVE: To determine if there are differences between men and women referred for treatment of osteoporosis in Canada. METHODS: We performed an observational study of 1588 patients (163 men, 1425 women), 50 years of age and older, who were prescribed cyclic etidronate or alendronate for treatment of osteoporosis or osteopenia and had at least 2 years of followup registered in the Canadian Database for Osteoporosis and Osteopenia Patients (CANDOO). Comparisons of characteristics between men and women were performed using Pearson chi-square test, Student's t test, or a Kruskal-Wallis test, whichever was most appropriate. RESULTS: Mean baseline femoral neck and lumbar spine bone mineral densities were significantly higher in men than women at both the femoral neck and lumbar spine (p < 0.05, respectively). Men had double the rate of prevalent vertebral fractures (44%, 72/163) compared to women (22%, 315/1425; p < 0.001) and triple the rate of multiple prevalent vertebral fractures (10%, 17/163) compared to women (3%, 37/1425, p < 0.001). Furthermore, men were twice as likely as women to sustain a fracture within 2 years of starting treatment during observation in the CANDOO study (men: 4%, 7/163, women: 2%, 24/1425, p = 0.033). CONCLUSION: Osteoporosis may be under-recognized in men until the condition is at an advanced stage. A form of gender bias may exist in recognition and treatment (or referral for treatment) of osteoporosis in men.

Siminoski K, Jiang G, Adachi JD, Hanley DA, Cline G, Ioannidis G, Hodsman A, Josse RG, Kendler D, Olszynski WP, Ste Marie LG, Eastell R. · Department of Radiology and Diagnostic Imaging and Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Alberta, Edmonton, Canada. · Osteoporos Int. · Pubmed #15309381 No free full text.

Abstract: Vertebral fractures are the most common type of osteoporotic fracture, but more than two-thirds remain undetected. We have examined the relationship between height loss and the development of new vertebral fractures to determine whether there is a height loss threshold that has useful clinical accuracy to detect new fractures. We studied 985 postmenopausal women with osteoporosis in the placebo arms of the Vertebral Efficacy with Risedronate Therapy studies. Height was measured annually for 3 years using a wall-mounted stadiometer. New fractures were determined using quantitative and semi-quantitative radiographic morphometry. The relationship between height loss over three years and the number of new vertebral fractures was: height loss (cm) = 0.95 x number of new vertebral fractures-0.4 cm (r = 0.33). The odds ratio for the development of a new fracture increased up to 20.6 (95% confidence interval, 9.3, 45.8) when height loss was greater than 4.0 cm. At a threshold of > 2.0 cm height loss over 3 years, sensitivity was 35.5% for detecting new vertebral fractures and specificity was 93.6%. These findings show that there is a strong relationship between the amount of height loss and the risk of a new vertebral fracture. While there is no cut-off that can reliably rule in a new fracture, height loss of < or = 2.0 cm over 1-3 years has acceptable accuracy for ruling out an incident fracture.