Simulated effects of early menopausal bone mineral density preservation on long-term fracture risk: a feasibility study.

Prevention of early menopausal bone loss may reduce the future burden of osteoporosis. In this modelling exercise, an osteoporosis prevention strategy involving 5-year infusions of zoledronic acid, beginning early in menopause, reduced long-term fracture risk and the proportion of aging women with femoral neck densitometric osteoporosis. This strategy warrants further evaluation. INTRODUCTION: Preventing early menopausal bone loss may substantially reduce the future burden of osteoporosis. We modelled the effects of infrequent zoledronic acid infusions on long-term fracture risk. METHODS: Data from the Canadian Multicentre Osteoporosis Study (CaMos) were used to determine the expected natural history of femoral neck areal bone mineral density (BMD) and fracture risk (using FRAX®) from ages 50-80 for women with no antiresorptive drug exposures. We modelled the effects of three infusions of zoledronic acid (at ages 50, 55, 60) on long-term fracture risk, assuming this intervention would preserve BMD until age 65 years, followed by losses mirroring early menopausal BMD loss. RESULTS: At age 65, untreated women and zoledronic acid recipients had expected mean (SD) femoral neck T-scores of - 1.5(1.0) and - 0.8(1.0), 10-year major osteoporotic fracture (MOF) risks of 9.8%(5.0) and 8.0%(3.7) and hip fracture risks of 1.7%(2.4) and 0.8%(1.2), respectively. At age 80, untreated women and zoledronic acid recipients had expected femoral neck T-scores of - 1.9(0.9) and - 1.4(0.9), MOF risks of 17.9%(8.2) and 14.9%(6.4) and hip fracture risks of 6.3%(6.2) and 4.4%(4.5), respectively. The expected proportion of women with femoral neck T-score ≤ - 2.5 was 14.9% for untreated women and 3.8% for zoledronic acid recipients at age 65, increasing to 28.1% and 12.0%, respectively, at age 80. Numbers-needed-to-treat to prevent one case of densitometric osteoporosis were 9 at age 65 and 5 at age 80. CONCLUSION: Infrequent infusions of zoledronic acid, initiated early in menopause, are expected to reduce long-term fracture risk and result in a substantial reduction in the proportion of women with densitometric osteoporosis after age 65.

Testing a theoretical model of imminent fracture risk in elderly women: an observational cohort analysis of the Canadian Multicentre Osteoporosis Study.

We examined the underlying relationship between fracture risk factors and their imminent risk. Results suggested that having past year fracture, worse past year general health, worse past year physical functioning, and lower past year BMD T-score directly predicted higher imminent fracture risk. Past year falls indirectly predicted imminent risk through physical functioning and general health. INTRODUCTION: This study aimed to examine direct and indirect effects of several factors on imminent (1 year) fracture risk. METHODS: Data from women age 65 and older from population-based Canadian Multicentre Osteoporosis Study were used. Predictors were identified from study years 5 and 10, and imminent fracture data (1-year fracture) came from years 6 and 11 (year 5 predicts year 6, year 10 predicts year 11). A structural equation model (SEM) was used to test the theoretical construct. General health and physical functioning were measured as latent variables using items from the 36-Item Short Form Health Survey (SF-36) and bone mineral density (BMD) T-score was a latent variable based on observed site-specific BMD data (spine L1-L4, femoral neck, total hip). Observed variables were fractures and falls. Model fit was evaluated using root mean square error of approximation (RMSEA), Tucker Lewis index (TLI), and comparative fit index (CFI). RESULTS: The analysis included 3298 women. Model fit tests showed that the SEM fit the data well; χ2(172) = 1122.10 < .001, RMSEA = .03, TLI = .99, CFI = .99. Results suggested that having past year fracture, worse past year general health, worse past year physical functioning, and lower past year BMD T-score directly predicted higher risk of fracture in the subsequent year (p < .001). Past year falls had a statistically significant but indirect effect on imminent fracture risk through physical functioning and general health (p < .001). CONCLUSIONS: We found several direct and indirect pathways that predicted imminent fracture risk in elderly women. Future studies should extend this work by developing risk scoring methods and defining imminent risk thresholds.

Longitudinal assessment of health-related quality of life in osteoporosis: data from the population-based Canadian Multicentre Osteoporosis Study.

Little is known about the association between health-related quality of life (HRQOL) and osteoporosis in the absence of fracture, and how HRQOL may change over time. This study provides evidence of substantially reduced HRQOL in women and men with self-reported and/or BMD-confirmed osteoporosis, even in the absence of fragility fracture. INTRODUCTION: Fragility fractures have a detrimental effect on the health-related quality of life (HRQOL) of those with osteoporosis. Less is known about the association between HRQOL and osteoporosis in the absence of fracture. METHODS: Canadian Multicentre Osteoporosis Study participants completed the SF-36, a detailed health questionnaire and measures of bone mineral density (BMD) at baseline and follow-up. We report the results of participants ≥ 50 years with 10-year follow-up. Self-reported osteoporosis at baseline and BMD-based osteoporosis at follow-up were ascertained. Multivariable linear regression models were developed for baseline SF-36 domains, component summaries, and change over time, adjusting for relevant baseline information. RESULTS: Baseline data were available for 5266 women and 2112 men. Women in the osteoporosis group had substantially lower SF-36 baseline scores, particularly in the physically oriented domains, than those without osteoporosis. A similar but attenuated pattern was evident for the men. After 10-year follow-up (2797 women and 1023 men), most domain scores dropped for women and men regardless of osteoporosis status, with the exception of mentally-oriented ones. In general, a fragility fracture was associated with lower SF-36 scores and larger declines over time. CONCLUSIONS: This study provides evidence of substantially reduced HRQOL in women and men with self-reported and/or BMD-confirmed osteoporosis, even in the absence of fragility fracture. HRQOL should be thoroughly investigated even prior to fracture, to develop appropriate interventions for all stages of the disease.

Longitudinal changes in calcium and vitamin D intakes and relationship to bone mineral density in a prospective population-based study: the Canadian Multicentre Osteoporosis Study (CaMos).

OBJECTIVES: Our objective was to study changes in calcium and vitamin D intakes over time, and their cross-sectional and longitudinal associations with bone mineral density (BMD). METHODS: We followed 9382 women and men aged ≥25 and 899 aged 16-24, for 10 and 2 years respectively. RESULTS: Calcium and vitamin D intakes increased over time in adults, but decreased in women aged 16-18. The increased intakes in adults were largely attributable to the increased use of calcium and/or vitamin D supplements. Both the percentage of supplement users and average dose among users increased over time. There was nevertheless a high prevalence of calcium and vitamin D intake below the estimated average requirement. At baseline, higher calcium and vitamin D intakes were associated with higher total hip and femoral neck BMD in young men, and cumulatively high levels of calcium and vitamin D intakes over time contributed to better BMD maintenance at lumbar spine and hip sites in adult women. CONCLUSIONS: Although total intakes, particularly of vitamin D, frequently fell below the Institute of Medicine recommendations despite an increase over time in supplement use, we found some positive associations between total calcium and vitamin D intake and bone health.

The effect of glucosamine on glucose metabolism in humans: a systematic review of the literature.

OBJECTIVE: Glucosamine is commonly used for the treatment of osteoarthritis. It is available as an over the counter preparation and also as a prescription pharmaceutical. There is concern from animal experiments that glucosamine may alter glucose metabolism through the hexosamine biosynthetic pathway. The objective of this systematic review is to determine if exogenous glucosamine adversely affects glucose metabolism in humans. This review does not separate out the effects on glucose metabolism of the various glucosamine preparations. METHOD: An English-language literature search of MEDLINE, EMBASE and EBM Reviews (1950-February 2009) was conducted. The bibliographies of selected papers were manually searched for additional references. Two reviewers independently analyzed studies for quality and content using a standardized data extraction form. RESULTS: Eleven studies were included. Six studies were randomized controlled trials and the remaining five were prospective studies with or without controls. Four of the studies found decreased insulin sensitivity or increased fasting glucose in subjects taking glucosamine. Three of these were clinical studies using oral glucosamine. Studies that included subjects with baseline impaired glucose tolerance or insulin resistance were more likely to detect an effect on glucose metabolism than studies without such subjects. CONCLUSION: Clinical studies, including three using oral glucosamine, have provided mixed evidence about the effect of exogenous glucosamine on glucose metabolism in humans. Therefore, more studies are needed, particularly including subjects at high risk for impairments in glucose homeostasis, before a definite conclusion can be made.

Fragility fractures and the osteoporosis care gap in women: the Canadian Multicentre Osteoporosis Study.

UNLABELLED: Canadian women over 50 years old were studied over a 10-year period to see if those who sustained a fracture (caused by minimal trauma) were receiving the recommended osteoporosis therapy. We found that approximately half of these women were not being treated, indicating a significant care gap in osteoporosis treatment. INTRODUCTION: Prevalent fragility fracture strongly predicts future fracture. Previous studies have indicated that women with fragility fractures are not receiving the indicated treatment. We aimed to describe post fracture care in Canadian women using a large, population-based prospective cohort that began in 1995-1997. METHODS: We followed 5,566 women over 50 years of age from across Canada over a period of 10 years in the Canadian Multicentre Osteoporosis Study. Information on medication use and incident clinical fragility fractures was obtained during a yearly questionnaire or interview and fractures were confirmed by radiographic/medical reports. RESULTS: Over the 10-year study period, 42-56% of women with yearly incident clinical fragility fractures were not treated with an osteoporosis medication. During year 1 of the study, 22% of the women who had experienced a fragility fracture were on treatment with a bisphosphonate and 26% were on hormone therapy (HT). We were not able to differentiate HT use for menopause symptoms vs osteoporosis. Use of bisphosphonate therapy increased over time; odds ratio (OR) for use at year 10 compared to use at year 1 was 3.65 (95% confidence interval (CI) 1.83-7.26). In contrast, HT use declined, with an OR of 0.07 (95%CI 0.02-0.24) at year 10 compared to year 1 of the study. CONCLUSION: In a large population-based cohort study, we found a therapeutic care gap in women with osteoporosis and fragility fractures. Although bisphosphonate therapy usage improved over time, a substantial gap remains.

The impact of incident fractures on health-related quality of life: 5 years of data from the Canadian Multicentre Osteoporosis Study.

UNLABELLED: 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.

A multifaceted intervention to improve treatment of osteoporosis in postmenopausal women with wrist fractures: a cluster randomized trial.

UNLABELLED: In a cluster randomized trial, we evaluated the effect of a multifaceted intervention (directed at both patient and primary care physician) on the rates of testing and treatment of osteoporosis in postmenopausal women within six months of their wrist fracture. Compared to usual care, women in the intervention practices were three times more likely to receive bone mineral density testing and prescribed osteoporosis treatments. INTRODUCTION: Postmenopausal women with wrist fractures are at increased risk of future fragility fractures, yet they frequently do not receive evaluation and treatment for osteoporosis. We set out to evaluate a multifaceted intervention designed to improve management of osteoporosis in older women with recent wrist fractures. METHODS: Cluster randomized trial of 270 women cared for in 119 primary care practices. We recruited postmenopausal women with an acute wrist fracture from the emergency departments of hospitals in southeastern Ontario, Canada. Family practices were randomly assigned to either the intervention or usual care. The intervention consisted of a mailed reminder with a summary of treatment guidelines and letter sent to the primary care physician, in addition to an educational package and letter to the women. The primary outcome was the proportion of women prescribed osteoporosis therapy within 6 months of their fracture. RESULTS: The mean age of women was 69(10.9) years. The intervention increased the proportion of women started on osteoporosis medications (28% vs. 10%) of controls, adjusted OR 3.45, 95% CI, 1.58-7.56, p = 0.002) and the proportion who had a bone mineral density (BMD) test (53.3% vs. 26%) of controls, OR 3.38, 95% CI, 1.83-6.26, p < 0.001). In addition to the intervention, having a female physician was a predictor of increased testing and treatment rates. CONCLUSION: A multifaceted intervention significantly improved rates of osteoporosis treatment and BMD testing in postmenopausal women with wrist fractures.

The osteoporosis care gap in men with fragility fractures: the Canadian Multicentre Osteoporosis Study.

UNLABELLED: 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.

Modulation of articular chondrocyte proliferation and anionic glycoconjugate synthesis by glucosamine (GlcN), N-acetyl GlcN (GlcNAc) GlcN sulfate salt (GlcN.S) and covalent glucosamine sulfates (GlcN-SO4).

OBJECTIVES: To investigate, in chondrocyte cultures under conditions for maximizing responses in proliferation and proteoglycan (PG) synthesis, the effects of glucosamine hydrochloride (GlcN.HCl) and glucosamine sulfate (GlcN.S) salts, N-acetyl glucosamine (GlcNAc), and covalently substituted GlcN-X,Y,Z(SO(4))(n) (general formula). METHODS: Bovine articular chondrocytes (BAC) were studied under anchorage-independent (AI, alginate beads) and anchorage-dependent (AD, plastic surface) conditions. Differentiation markers were evaluated (e.g., cartilage-specific (V+C)(-) fibronectin). Varying concentrations of GlcN.HCl, GlcN.S, GlcNAc and GlcN sulfated at positions -2, -3, -6, (-2,3), (-3,6) and (-3,4,6), were tested. Cell proliferation, DNA synthesis and [(35)S]-sulfate incorporation into newly synthesized PG were determined. RESULTS: Increasing GlcN.HCl or GlcN.S concentrations gave decreasing net PG synthesis. Compounds showed more pronounced effects in AD cultures (expressing the V(-)C(+) fibronectin isoform) compared to AI cultures ((V+C)(-) isoform). Addition of GlcN.HCl or GlcN.S gave a concentration-dependent decrease in BAC proliferation, partially prevented by glucose (Glc). GlcNAc was not inhibitory. Addition of GlcN-2-SO(4) or GlcN-2,6-diSO(4) did not affect proliferation or DNA synthesis. The other GlcN-sulfates gave varying inhibitory effects, which for GlcN-3-SO(4) were reversed by inosine. CONCLUSIONS: The free amino group of GlcN seems responsible for inhibition of chondrocyte proliferation and PG synthesis. These effects were greater under higher concentrations of GlcN in AD vs AI conditions. GlcN.HCl behaves similarly to GlcN.S, but differential effects with GlcN-X,Y,Z(SO(4))(n) isomers were observed. Acetylation or sulfation of the GlcN amino group reverses or partially reverses, respectively, anti-proliferative effects of GlcN. Sulfation of GlcN, at positions 3 and 6 results in complex effects on AC proliferation and PG synthesis.

The action of TNFalpha and TGFbeta include specific alterations of the glycosylation of bovine and human chondrocytes.

Joint destruction in arthritis is often associated with high levels of inflammatory cytokines. Previous work has shown that inflammatory conditions can alter the activities of glycosyltransferases that synthesize the glycan chains of glycoproteins, and that these changes in turn can influence the functions of glycoproteins. We therefore examined glycosyltransferases involved in glycoprotein biosynthesis in primary cultures of bovine articular chondrocytes and human chondrocytes isolated from knee cartilage of osteoarthritis patients. Bovine chondrocytes exhibited enzyme activities involved in the synthesis of bi-antennary complex Asn-linked N-glycans, as well as the enzymes involved in the synthesis of GalNAc-Ser/Thr-linked O-glycans with the core 1 structure. Human chondrocytes, in addition, were able to synthesize more complex O-glycans with core 2 structures. TNFalpha was found to induce apoptosis in chondrocytes, and this process was associated with significant changes in lectin binding to chondrocyte cell surface glycans. TGFbeta increased cell proliferation, and had significant effects on cell surface glycosylation in bovine but not in human cells. These cytokine-specific effects were partially correlated with changes in glycosyltransferase activities. Thus, chondrocytes have many of the enzymes necessary for the synthesis of N- and O-glycan chains of glycoproteins. The O-glycosylation pathways and the effects of TNFalpha and TGFbeta on glycosylation differed between bovine and human chondrocytes. These alterations are of potential importance for the regulation of the functions of cell surface receptors on chondrocytes, and for an understanding of the pathophysiology of arthritis.

Prevalence of and factors associated with glucosamine use in Canada.

OBJECTIVE: Glucosamine is commonly used for the treatment of osteoarthritis, and its use is increasing in the general population. The Canadian Multicentre Osteoporosis Study (CaMos) provided an opportunity to examine the prevalence of glucosamine use across age and gender groups, and to assess the factors associated with its use. METHOD: CaMos is a random, population-based sample of 9423 Canadians. Baseline assessments took place in 1996-1997 and the 5-year follow-up assessments in 2001-2002. The primary outcome of this analysis was glucosamine use at year 5. Prevalence estimates were age- and sex-standardized to the Canadian population. A number of factors potentially associated with glucosamine use were identified from the literature. Multivariable logistic regression was used to identify variables associated with glucosamine use. RESULTS: At 5 years, complete data were available for 7652 of the original 9423 participants (81.2%). For men, glucosamine use increased from 0.9% to 4.7% (weighted values), and for women, it increased from 1.3% to 8.2%. Glucosamine use was higher among older participants, those living in western Canada, and those with arthritis, back pain, higher calcium intake from supplements, physical activity and prior glucosamine use. CONCLUSIONS: Glucosamine use increased substantially over 5 years, and its use is associated with a number of factors. Some may use glucosamine to manage pain and symptoms of arthritis and back pain, while others use it as a preventive measure to maintain health.

Glucosamine therapy for treating osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is the most common form of arthritis, and it is often associated with significant disability and an impaired quality of life. OBJECTIVES: To review all randomized controlled trials (RCTs) evaluating the effectiveness and toxicity of glucosamine in OA. SEARCH STRATEGY: We searched MEDLINE, PREMEDLINE, EMBASE, AMED, ACP Journal Club, DARE, CDSR, and the CCTR. We also wrote letters to content experts, and hand searched reference lists of identified RCTs and pertinent review articles. All searches were updated in January 2005. SELECTION CRITERIA: Relevant studies met the following criteria: 1) RCTs evaluating the effectiveness and safety of glucosamine in OA, 2) Both placebo controlled and comparative studies were eligible, 3) Both single blinded and double blinded studies were eligible. DATA COLLECTION AND ANALYSIS: Data abstraction was performed independently by two investigators and the results were compared for degree of agreement. Gotzsche's method and a validated tool (Jadad 1996) were used to score the quality of the RCTs. Continuous outcome measures were pooled using standardized mean differences (SMD) as the measure of effect size. Dichotomous outcome measures were pooled using relative risk ratios (RR). MAIN RESULTS: Analysis restricted to eight studies with adequate allocation concealment failed to show benefit of glucosamine for pain and WOMAC function. Collectively, the 20 analyzed RCTs found glucosamine favoured placebo with a 28% (change from baseline) improvement in pain (SMD -0.61, 95% CI -0.95, -0.28) and a 21% (change from baseline) improvement in function using the Lequesne index (SMD -0.51 95% CI -0.96, -0.05). However, the results are not uniformly positive, and the reasons for this remain unexplained. WOMAC pain, function and stiffness outcomes did not reach statistical significance. In the 10 RCTs in which the Rotta preparation of glucosamine was compared to placebo, glucosamine was found to be superior for pain (SMD -1.31, 95% CI -1.99, -0.64) and function using the Lequesne index (SMD -0.51, 95% CI -0.96, -0.05). Pooled results for pain (SMD -0.15, 95% CI -0.35, 0.05) and function using the WOMAC index (SMD 0.03, 95% CI -0.18, 0.25) in those RCTs in which a non-Rotta preparation of glucosamine was compared to placebo did not reach statistical significance. In the four RCTs in which the Rotta preparation of glucosamine was compared to an NSAID, glucosamine was superior in two, and equivalent in two. Two RCTs using the Rotta preparation showed that glucosamine was able to slow radiological progression of OA of the knee over a three year period (SMD 0.24, 95% CI 0.04, 0.43). Glucosamine was as safe as placebo in terms of the number of subjects reporting adverse reactions (RR=0.97, 95% CI, 0.88, 1.08). AUTHORS' CONCLUSIONS: This update includes 20 studies with 2570 patients. Pooled results from studies using a non-Rotta preparation or adequate allocation concealment failed to show benefit in pain and WOMAC function while those studies evaluating the Rotta preparation show that glucosamine was superior to placebo in the treatment of pain and functional impairment resulting from symptomatic OA. WOMAC outcomes of pain, stiffness and function did not show a superiority of glucosamine over placebo for both Rotta and non-Rotta preparations of glucosamine. Glucosamine was as safe as placebo.

Artefacts in the mechanical characterization of porcine articular cartilage due to freezing.

Many experimental protocols for investigating articular cartilage mechanics have involved the use of a freeze-thaw cycle for storage or tissue manipulation. It was hypothesized that mechanical properties are altered due to freeze-thaw cycling. The aim of this study, therefore, was to examine the possibility of protocol-induced artefacts in the mechanical properties of porcine articular cartilage specimens related specifically to freeze-thaw events. Twenty-eight osteochondral specimens [14 from the femoral condyles (FCs) and 14 from the patella-femoral (PF) groove] were tested in confined compression before and after being frozen at -20 degrees C for 7 days. The fluid-independent and fluid-dependent mechanical properties (aggregate modulus of the solid phase and the half-life of stress relaxation respectively) were determined and compared. The aggregate modulus decreased by 13.5 per cent and 20.1 per cent for the PF and FC regions respectively (p = 0.002) and the half-life of the stress relaxation at 10 per cent strain decreased by 6.4 per cent and 12.6 per cent for the PF and FC specimens respectively (p = 0.0341). In conclusion, it has been shown that the protocol used, which involved freezing to -20 degrees C and thawing after 7 days, caused artefacts in the mechanical properties of porcine osteochondral specimens. It is suggested that protocols requiring freezing must be critically reviewed to eliminate such artefacts.

The association between osteoporotic fractures and health-related quality of life as measured by the Health Utilities Index in the Canadian Multicentre Osteoporosis Study (CaMos).

Osteoporotic fractures can be a major cause of morbidity. It is important to determine the impact of fractures on health-related quality of life (HRQL). A total of 3,394 women and 1,122 men 50 years of age and older, who were recruited for the Canadian Multicentre Osteoporosis Study (CaMos), participated in this cross-sectional study. Minimal trauma fractures of the hip, pelvis, spine, lower body (included upper and lower leg, knee, ankle, and foot), upper body (included arm, elbow, sternum, shoulder, and clavicle), wrist and hand (included forearm, hand, and finger), and ribs were studied. Participants with subclinical vertebral deformities were also examined. The Health Utilities Index Mark II and III Systems were used to assess HRQL. Past osteoporotic fractures varied in prevalence from 1.2% (pelvis) to 27.8% (lower body) in women and 0.3% (pelvis) to 29.3% (wrist) in men. Multivariate linear regression analyses [parameter estimates and corresponding 95% confidence intervals (CI)] indicated that minimal trauma fractures were negatively associated with HRQL and that this relationship depends on fracture type and gender. The multi-attribute scores for the Mark II system were negatively related to hip (-0.05; 95% CI: -0.09, -0.01), lower body (-0.02; 95% CI: -0.03, -0.000), and subclinical vertebral fractures (-0.02; 95% CI: -0.03, -0.00) for women. The multi-attribute scores for the Mark III system were negatively related to hip (-0.09; 95% CI: -0.14, -0.03) and rib fractures (-0.06; 95% CI: -0.11, -0.00) for women, and rib fractures (-0.06; 95% CI: -0.12, -0.00) for men. In conclusion, this study demonstrates a negative association between osteoporotic fractures and quality of life in both women and men.

Associations among disease conditions, bone mineral density, and prevalent vertebral deformities in men and women 50 years of age and older: cross-sectional results from the Canadian Multicentre Osteoporosis Study.

This cross-sectional cohort study of 5566 women and 2187 men 50 years of age and older in the population-based Canadian Multicentre Osteoporosis Study was conducted to determine whether reported past diseases are associated with bone mineral density or prevalent vertebral deformities. We examined 12 self-reported disease conditions including diabetes mellitus (types 1 or 2), nephrolithiasis, hypertension, heart attack, rheumatoid arthritis, thyroid disease, breast cancer, inflammatory bowel disease, neuromuscular disease, Paget's disease, and chronic obstructive pulmonary disease. Multivariate linear and logistic regression analyses were performed to determine whether there were associations among these disease conditions and bone mineral density of the lumbar spine, femoral neck, and trochanter, as well as prevalent vertebral deformities. Bone mineral density measurements were higher in women and men with type 2 diabetes compared with those without after appropriate adjustments. The differences were most notable at the lumbar spine (+0.053 g/cm2), femoral neck (+0.028 g/cm2), and trochanter (+0.025 g/cm2) in women, and at the femoral neck (+0.025 g/cm2) in men. Hypertension was also associated with higher bone mineral density measurements for both women and men. The differences were most pronounced at the lumbar spine (+0.022 g/cm2) and femoral neck (+0.007 g/cm2) in women and at the lumbar spine (+0.028 g/cm2) in men. Although results were statistically inconclusive, men reporting versus not reporting past nephrolithiasis appeared to have clinically relevant lower bone mineral density values. Bone mineral density differences were -0.022, -0.015, and -0.016 g/cm2 at the lumbar spine, femoral neck, and trochanter, respectively. Disease conditions were not strongly associated with vertebral deformities. In summary, these cross-sectional population-based data show that type 2 diabetes and hypertension are associated with higher bone mineral density in women and men, and nephrolithiasis may be associated with lower bone mineral density in men. The importance of these associations for osteoporosis case finding and management require further and prospective studies.

Positive effect of etidronate therapy is maintained after drug is terminated in patients using corticosteroids.

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.

Glucosamine therapy for treating osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is the most common form of arthritis, and it is often associated with significant disability and an impaired quality of life. OBJECTIVES: To review all randomized controlled trials (RCTs) evaluating the effectiveness and toxicity of glucosamine in osteoarthritis (OA). SEARCH STRATEGY: We searched MEDLINE, Embase, and Current Contents up to November 1999, and the Cochrane Controlled Trials Register. We also wrote letters to content experts, and hand searched reference lists of identified RCTs and pertinent review articles. SELECTION CRITERIA: Relevant studies met the following criteria: 1) RCTs evaluating the effectiveness and safety of glucosamine in OA, 2) Both placebo based and comparative studies were eligible, 3) Both single blinded and double-blinded studies were eligible. DATA COLLECTION AND ANALYSIS: Data abstraction was performed independently by two investigators and the results were compared for degree of agreement. Gotzsche's method and a validated tool (Jadad 1995) were used to score the quality of the RCTs. Continuous outcome measures were pooled using standardized mean differences. Dichotomous outcome measures were pooled using Peto Odds Ratios. MAIN RESULTS: Collectively, the 16 identified RCTs provided evidence that glucosamine is both effective and safe in OA. In the 13 RCTs in which glucosamine was compared to placebo, glucosamine was found to be superior in all RCTs, except one. In the four RCTs in which glucosamine was compared to an NSAID, glucosamine was superior in two, and equivalent in two. REVIEWER'S CONCLUSIONS: Further research is necessary to confirm the long term effectiveness and toxicity of glucosamine therapy in OA. Most of the trials reviewed only evaluated the Rotta preparation of glucosamine sulfate. It is not known whether different glucosamine preparations prepared by different manufacturers are equally effective in the therapy of OA.

The influence of osteoporotic fractures on health-related quality of life in community-dwelling men and women across Canada.

Health-related quality of life (HRQL) was examined in relation to prevalent fractures in 4816 community-dwelling Canadian men and women 50 years and older participating in the Canadian Multicentre Osteoporosis Study (CaMos). Fractures were of three categories: clinically recognized main fractures, subclinical vertebral fractures and fractures at other sites. Main fractures were divided and analyzed at the hip, spine, wrist/forearm, pelvis and rib sites. Baseline assessments of anthropometric data, medical history, therapeutic drug use, spinal radiographs and prevalent fractures were obtained from all participants. The SF-36 instrument was used as a tool to measure HRQL. A total of 652 (13.5%) main fractures were reported. Results indicated that hip, spine, wrist/forearm, pelvis and rib fractures had occurred in 78 (1.6%), 40 (0.8%), 390 (8.1%), 19 (0.4%) and 125 (2.6%) individuals, respectively (subjects may have had more than one main fracture). Subjects who had experienced a main prevalent fracture had lower HRQL scores compared with non-fractured participants. The largest differences were observed in the physical functioning (-4.0; 95% confidence intervals (CI): -6.0, -2.0) and role-physical functioning domains (-5.8; 95% CI: -9.5, -2.2). In women, the physical functioning domain was most influenced by hip (-14.9%; 95% CI: -20.9, -9.0) and pelvis (-18.1; 95% CI: -27.6, -8.6) fractures. In men, the role-physical domain was most affected by hip fractures (-35.7; 95% CI: -60.4, -11.1). Subjects who experienced subclinical vertebral fractures had lower HRQL scores than those without prevalent fractures. In conclusion, HRQL was lower in the physical functioning domain in women and the role-physical domain in men who sustained main fractures at the hip. Subclinical vertebral fractures exerted a moderate effect on HRQL.

Differential use of Alcian blue and toluidine blue dyes for the quantification and isolation of anionic glycoconjugates from cell cultures: application to proteoglycans and a high-molecular-weight glycoprotein synthesized by articular chondrocytes.

Alcian blue and toluidine blue dyes form complexes with anionic glycoconjugates (AG) such as proteoglycans (PG) and glycosaminoglycans (GAG). However, the Alcian blue-AG complexes do not readily dissociate, while the toluidine blue-AG complexes do so in salt solutions. This differential dissociation of the dye-AG complexes has been utilized in the analysis and isolation of radiolabeled AG elaborated by articular chondrocyte cultures incubated with the radiolabeled precursors of AG. For the rapid quantification of newly synthesized (35)S-labeled PG, small replicate aliquots of the radiolabeled culture media were applied directly to cellulose acetate strips, stained with Alcian blue and the stained immobilized radiolabeled PG was quantified by liquid scintillation counting. Comparison of anionic glycoconjugates quantified in the culture media employing toluidine blue and Alcian blue staining on cellulose acetate trips gave similar results. Staining on cellulose acetate strips using these two dyes is particularly suited for the simultaneous processing of large numbers of samples, as illustrated by the screening of the effects of biological materials and drugs on AG synthesis, in cultures labeled with [(35)S]-sulfate and [(3)H]-glucosamine. The Alcian blue and toluidine blue precipitation methods yielded similar results for the total AG recovered from the media of TGF-beta-stimulated chondrocytes. Electrophoretic analysis of toluidine blue- and Alcian blue-precipitated AG followed by autoradiography and Alcian blue staining in combination with silver nitrate demonstrated that both dyes yielded similar pattern of bands on gels. However, some AG from Alcian blue precipitate did not enter the gel, suggesting incomplete dissociation of Alcian blue-AG complex. The application of the toluidine blue precipitation method, in combination with enzymatic digestion of the GAG chains of the PGs, is illustrated by the isolation of a non-PG high-molecular-weight AG, as well as the PGs from the media of chondrocyte cultures stimulated by TGF-beta.