Bone loss with antiepileptic drug therapy: a twin and sibling study.

Changes in areal bone mineral density (aBMD) and other predictors of bone loss were evaluated in 48 same-sex twin/age-matched sibling pairs discordant for antiepileptic drug (AED) use. AED users had reduced BMD at the hip regions. Prolonged AED users had greater aBMD loss, predicting a higher risk of bone fragility. INTRODUCTION: To investigate the longitudinal associations of bone mineral measures with antiepileptic drug (AED) use, including enzyme-inducing (EIAED) and non-enzyme-inducing (NEIAED) types, and other predictors of bone loss in a study of 48 same-sex twin/age-matched sibling pairs (40 female, 8 male) discordant for AED use. METHODS: Using dual-energy X-ray absorptiometry (DXA), areal bone mineral density (aBMD) and content (BMC) at the hip regions, forearm, lumbar spine, and whole body were measured twice, at least 2 years apart. The mean within-pair difference (MWPD), MWPD%, and mean annual rate of aBMD change were adjusted for age, weight, and height. Predictors of bone loss were evaluated. RESULTS: AED users, compared to non-users, at baseline and follow-up, respectively, had reduced aBMD at the total hip (MWPD% 3.8, 4.4%), femoral neck (4.7, 4.5%), and trochanter regions (4.1, 4.6%) (p < 0.05). For the whole cohort, the annual rate of change in all aBMD/BMC (p > 0.05) regions did not differ within pairs. Nevertheless, EIAED users had greater aBMD loss than non-users (n = 20 pairs) at the total hip (1.7 vs. 0.3%, p = 0.013) and whole body regions (0.7% loss vs. 0.1% BMD gain, p = 0.019), which was not found in NEIAED-discordant pairs (n = 16). AED use >20 years predicted higher aBMD loss at the forearm (p = 0.028), whole body (p = 0.010), and whole body BMC (p = 0.031). CONCLUSIONS: AED users had reduced aBMD at the hip regions. Prolonged users and EIAED users had greater aBMD loss, predicting a higher risk of bone fragility. Further prospective studies of AED effects on bone microarchitecture are needed.

Non-hip, non-spine fractures drive healthcare utilization following a fracture: the Global Longitudinal Study of Osteoporosis in Women (GLOW).

UNLABELLED: We evaluated healthcare utilization associated with treating fracture types in >51,000 women aged ≥55 years. Over the course of 1 year, there were five times more non-hip, non-spine fractures than hip or spine fractures, resulting in twice as many days of hospitalization and rehabilitation/nursing home care for non-hip, non-spine fractures. INTRODUCTION: The purpose of this study is to evaluate medical healthcare utilization associated with treating several types of fractures in women ≥55 years from various geographic regions. METHODS: Information from the Global Longitudinal Study of Osteoporosis in Women (GLOW) was collected via self-administered patient questionnaires at baseline and year 1 (n = 51,491). Self-reported clinically recognized low-trauma fractures at year 1 were classified as incident spine, hip, wrist/hand, arm/shoulder, pelvis, rib, leg, and other fractures. Healthcare utilization data were self-reported and included whether the fracture was treated at a doctor's office/clinic or at a hospital. Patients were asked if they had undergone surgery or been treated at a rehabilitation center or nursing home. RESULTS: During 1-year follow-up, there were 195 spine, 134 hip, and 1,654 non-hip, non-spine fractures. Clinical vertebral fractures resulted in 617 days of hospitalization and 512 days of rehabilitation/nursing home care; hip fractures accounted for 1,306 days of hospitalization and 1,650 days of rehabilitation/nursing home care. Non-hip, non-spine fractures resulted in 3,805 days in hospital and 5,186 days of rehabilitation/nursing home care. CONCLUSIONS: While hip and vertebral fractures are well recognized for their associated increase in health resource utilization, non-hip, non-spine fractures, by virtue of their 5-fold greater number, require significantly more healthcare resources.

An appendix to the 2012 IOF-ECTS guidelines for the management of glucocorticoid-induced osteoporosis.

The use of glucocorticoids in the treatment of medical disorders can lead to rapid bone loss and increased risk of fragility fracture. Updated clinical guidelines are needed that accommodate recent advances in fracture risk assessment and new pharmacological interventions to reduce fracture risk. This document serves as an appendix to the 2012 IOF-ECTS guidelines for the management of glucocorticoid-induced osteoporosis.

Burden of non-hip, non-vertebral fractures on quality of life in postmenopausal women: the Global Longitudinal study of Osteoporosis in Women (GLOW).

UNLABELLED: Among 50,461 postmenopausal women, 1,822 fractures occurred (57% minor non-hip, non-vertebral [NHNV], 26% major NHNV, 10% spine, 7% hip) over 1 year. Spine fractures had the greatest detrimental effect on EQ-5D, followed by major NHNV and hip fractures. Decreases in physical function and health status were greatest for spine or hip fractures. INTRODUCTION: There is growing evidence that NHNV fractures result in substantial morbidity and healthcare costs. The aim of this prospective study was to assess the effect of these NHNV fractures on quality of life. METHODS: We analyzed the 1-year incidences of hip, spine, major NHNV (pelvis/leg, shoulder/arm) and minor NHNV (wrist/hand, ankle/foot, rib/clavicle) fractures among women from the Global Longitudinal study of Osteoporosis in Women (GLOW). Health-related quality of life (HRQL) was analyzed using the EuroQol EQ-5D tool and the SF-36 health survey. RESULTS: Among 50,461 women analyzed, there were 1,822 fractures (57% minor NHNV, 26% major NHNV, 10% spine, 7% hip) over 1 year. Spine fractures had the greatest detrimental effect on EQ-5D summary scores, followed by major NHNV and hip fractures. The number of women with mobility problems increased most for those with major NHNV and spine fractures (both +8%); spine fractures were associated with the largest increases in problems with self care (+11%), activities (+14%), and pain/discomfort (+12%). Decreases in physical function and health status were greatest for those with spine or hip fractures. Multivariable modeling found that EQ-5D reduction was greatest for spine fractures, followed by hip and major/minor NHNV. Statistically significant reductions in SF-36 physical function were found for spine fractures, and were borderline significant for major NHNV fractures. CONCLUSION: This prospective study shows that NHNV fractures have a detrimental effect on HRQL. Efforts to optimize the care of osteoporosis patients should include the prevention of NHNV fractures.

A framework for the development of guidelines for the management of glucocorticoid-induced osteoporosis.

UNLABELLED: This paper provides a framework for the development of national guidelines for the management of glucocorticoid-induced osteoporosis in men and women aged 18 years and over in whom oral glucocorticoid therapy is considered for 3 months or longer. INTRODUCTION: The need for updated guidelines for Europe and other parts of the world was recognised by the International Osteoporosis Foundation and the European Calcified Tissue Society, which set up a joint Guideline Working Group at the end of 2010. METHODS AND RESULTS: The epidemiology of GIO is reviewed. Assessment of risk used a fracture probability-based approach, and intervention thresholds were based on 10-year probabilities using FRAX. The efficacy of intervention was assessed by a systematic review. CONCLUSIONS: Guidance for glucocorticoid-induced osteoporosis is updated in the light of new treatments and methods of assessment. National guidelines derived from this resource need to be tailored within the national healthcare framework of each country.

Does increased sunlight exposure work as a strategy to improve vitamin D status in the elderly: a cluster randomised controlled trial.

SUMMARY: Sunlight exposure by improving vitamin D status could be a simple public health strategy in reducing falls among frail elder people. In a randomised controlled trial, adherence to sunlight exposure was low (median adherence, 26%) and no effect of increased UV exposure on falls risk was observed (incidence rate ratio (IRR) 1.06, P = 0.73). INTRODUCTION: This study aimed to determine whether increased sunlight exposure was effective to improve vitamin D status and reduce falls in the elderly. METHODS: In a cluster randomised controlled trial (NCT00322166 at ClinicalTrials.gov), 602 residents aged 70 or more (mean age, 86.4 years; 71% female) were recruited from 51 aged care facilities in Northern Sydney, Australia. Participants were randomised by facility to receive either increased sunlight exposure (additional 30-40 min/day in the early morning) with (UV+) or without (UV) calcium supplementation (600 mg/day) or neither (control) for a year. The co-primary endpoints were change in serum 25 hydroxy vitamin D (25OHD) and falls incidence after 12 months. RESULTS: Adherence to sunlight exposure was low (median adherence, 26%; IQR, 7%-45%). Serum 25OHD levels were low at baseline (median, 32.9 nmol/L) and increased only slightly depending on the number of sunlight sessions attended over 12 months (P = 0.04). During the study, 327 falls occurred in 111 (54%) subjects in the control group, 326 falls in 111 (58%) subjects in the UV only group and 335 falls in 108 (52%) subjects in the UV+ group. By intention-to-treat analysis, there was no significant effect of increased UV exposure on falls risk (IRR, 1.06; 95% CI, 0.76-1.48; P = 0.73). However, in 66 participants who attended ≥130 sessions per year (adherence, ≥50% of 260 sessions-five per week), falls were significantly reduced (IRR, 0.52; 95% CI, 0.31-0.88; P = 0.01) compared with the control group. CONCLUSIONS: Increased sunlight exposure did not reduce vitamin D deficiency or falls risk in frail older people. This public health strategy was not effective most likely due to poor adherence to the intervention.

Post hoc analysis of a single IV infusion of zoledronic acid versus daily oral risedronate on lumbar spine bone mineral density in different subgroups with glucocorticoid-induced osteoporosis.

This study summarizes the treatment effect of zoledronic acid infusion on lumbar spine bone mineral density in different subgroups with glucocorticoid-induced osteoporosis. Zoledronic acid is significantly more effective than risedronate in increasing lumbar spine (LS) bone mineral density (BMD) in both prevention and treatment of glucocorticoid-induced osteoporosis. Introduction In patients on glucocorticoids, a single zoledronic acid infusion significantly increased BMD versus daily oral risedronate. We assessed treatment effect on LS BMD in different patient subgroups at month 12 that contributed to the risk of osteoporosis in addition to glucocorticoids. Methods Patients randomized to a single IV infusion of zoledronic acid 5 mg or risedronate (5 mg/day) and stratified based on glucocorticoids duration [treatment (>3 months) and prevention (≤ 3 months) subpopulations]were subgrouped by age; gender; menopausal status in women; dose and duration of prednisone during the trial; and baseline serum 25-OH vitamin D, LS BMD T-score, creatinine clearance, and concomitant medication use. Results At month 12, zoledronic acid significantly increased LS BMD versus risedronate in patients ≤ 74 years (P<0.05) in the treatment and 65-74 years (P = 0.0008) in the prevention subpopulation. At month 12, zoledronic acid significantly increased LS BMD versus risedronate in both subpopulations irrespective of gender (all P<0.05), cumulative prednisone dose (all P<0.01), and postmenopausal status (all P<0.05). In premenopausal women, in both subpopulations, zoledronic acid significantly increased total hip BMD (all P<0.05) versus risedronate at month 12 but not LS BMD. Osteoporotic patients in the prevention (P=0.0189) and osteopenic patients in the treatment subpopulation (P=0.0305) showed significant LS BMD increases with zoledronic acid versus risedronate at month 12. Conclusions This post hoc analysis suggests that zoledronic acid is significantly more effective than risedronate in increasing LS BMD in prevention and treatment of glucocorticoid-induced osteoporosis across a wide range of patients.

Regional and age-related variations in the proportions of hip fractures and major fractures among postmenopausal women: the Global Longitudinal Study of Osteoporosis in Women.

UNLABELLED: We examined variations in proportions of hip fractures and major fractures among postmenopausal women using the Global Longitudinal Study of Osteoporosis in Women (GLOW). The proportion of major fractures that were hip fractures varied with age and region, whereas variations in the proportion of fractures that were major fractures appeared modest. INTRODUCTION: In many countries, the World Health Organization fracture risk assessment tool calculates the probability of major fractures by assuming a uniform age-associated proportion of major fractures that are hip fractures in different countries. We further explored this assumption, using data from the GLOW. METHODS: GLOW is an observational population-based study of 60,393 non-institutionalized women aged ≥55 years who had visited practices within the previous 2 years. Main outcome measures were self-reported prevalent fractures after the age of 45 years and incident fractures during the 2 years of follow-up. RESULTS: The adjusted proportion of prevalent and incident major fractures after the age of 45 years that were hip fractures was higher in North America (16%, 17%) than in northern (13%, 12%) and southern Europe (10%, 10%), respectively. The proportion of incident major fractures that were hip fractures increased more than five-fold with age, from 6.6% among 55-59-year-olds to 34% among those aged ≥85 years. Regional and age-associated variations in the proportion of all incident fractures that were major fractures were less marked, not exceeding 16% and 28%, respectively. CONCLUSIONS: The data suggest that there may be regional differences in the proportion of major fractures that are hip fractures in postmenopausal women. In contrast, the regional and age-related variations in the proportion of fractures that are major fractures appear to be modest. However, because of the limited number of fractures in our sample, further studies are necessary to confirm these findings.

Weight loss in obese people has structure-modifying effects on medial but not on lateral knee articular cartilage.

BACKGROUND: Obesity is an important risk factor for knee osteoarthritis (OA), Weight loss can reduce the symptoms of knee OA. No prospective studies assessing the impact of weight loss on knee cartilage structure and composition have been performed. OBJECTIVES: To assess the impact of weight loss on knee cartilage thickness and composition. METHODS: 111 obese adults were recruited from either laparoscopic adjustable gastric banding or exercise and diet weight loss programmes from two tertiary centres. MRI was performed at baseline and 12-month follow-up to assess cartilage thickness. 78 eligible subjects also underwent delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), an estimate of proteoglycan content. The associations between cartilage outcomes (cartilage thickness and dGEMRIC index) and weight loss were adjusted for age, gender, body mass index (BMI) and presence of clinical knee OA. RESULTS: Mean age was 51.7 ± 11.8 years and mean BMI was 36.6 ± 5.8 kg/m(2); 32% had clinical knee OA. Mean weight loss was 9.3 ± 11.9%. Percentage weight loss was negatively associated with cartilage thickness loss in the medial femoral compartment in multiple regression analysis (ß=0.006, r(2)=0.19, p=0.029). This association was not detected in the lateral compartment (r(2)=0.12, p=0.745). Percentage weight loss was associated with an increase in medial dGEMRIC in multiple regression analysis (ß=3.9, r(2)=0.26; p=0.008) but not the lateral compartment (r(2)=0.14, p=0.34). For every 10% weight loss there was a gain in the medial dGEMRIC index of 39 ms (r(2)=0.28; p=0.014). The lowest weight loss cut-off associated with reduced medial femoral cartilage thickness loss and improved medial dGEMRIC index was 7%. CONCLUSIONS: Weight loss is associated with improvements in the quality (increased proteoglycan content) and quantity (reduced cartilage thickness losses) of medial articular cartilage. This was not observed in the lateral compartment. This could ultimately lead to a reduced need for total joint replacements and is thus a finding with important public health implications.

Neck and back pain and intervertebral disc degeneration: role of occupational factors.

Back pain is a near-universal human experience at some time during life, and neck pain is also common. The overwhelming majority of low back and cervical pain is considered to be due to unspecified mechanical factors or disc degeneration, which is a common with ageing and, hence, in people of working age. Back pain and disc disease appear to have significant heritability, based upon twin studies, but environmental factors also contribute - including physical occupational activities in some studies - although the strength of this association remains uncertain. This article examines the contribution of genetic and environmental factors to back pain and disc disease, with a specific focus on occupational exposures.

Increased chondrocyte sclerostin may protect against cartilage degradation in osteoarthritis.

OBJECTIVES: To investigate the regulation of sclerostin (SOST) in osteoarthritis (OA) and its potential effects on articular cartilage degradation. METHODS: SOST and other Wnt-ß-catenin components were immuno-localised in osteochondral sections of surgically-induced OA in knees of sheep and mice, and human OA samples obtained at arthroplasty. Regulation of SOST mRNA and protein expression by ovine chondrocytes in response to interleukin-1α (IL-1α) or tumour necrosis factor-α (TNFα) was examined in explant cultures. The effect of 25 or 250 ng/ml recombinant SOST alone or in combination with IL-1α, on ovine articular cartilage explant aggrecan degradation, and chondrocyte gene expression of Wnt-ß-catenin pathway proteins, metalloproteinases and their inhibitors, and cartilage matrix proteins was quantified. RESULTS: Contrary to being an osteocyte-specific protein, SOST was expressed by articular chondrocytes, and mRNA levels were upregulated in vitro by IL-1α but not TNFα. Chondrocyte SOST staining was significantly increased only in the focal area of cartilage damage in surgically-induced OA in sheep and mice, as well as end-stage human OA. In contrast, osteocyte SOST was focally decreased in the subchondral bone in sheep OA in association with bone sclerosis. SOST was biologically active in chondrocytes, inhibiting Wnt-ß-catenin signalling and catabolic metalloproteinase [matrix metalloproteinases (MMP) and distintegrin and metalloproteinase with thrombospndin repeats (ADAMTS)] expression, but also decreasing mRNA levels of aggrecan, collagen II and tissue inhibitors of metalloproteinaes (TIMPs). Despite this mixed effect, SOST dose-dependently inhibited IL-1α-stimulated cartilage aggrecanolysis in vitro. CONCLUSIONS: These results implicate SOST in regulating the OA disease processes, but suggest opposing effects by promoting disease-associated subchondral bone sclerosis while inhibiting degradation of cartilage.

Intrusive pain and worry about health in older men: the CHAMP study.

The role of anxiety in pain is less well understood than the role of depression. Based on recent conceptual thinking about worry and pain, we explored the relationship between pain status and worry about health and anxiety in 1217 community-dwelling men aged 70 years or older who participated in the baseline phase of the Concord Health and Ageing in Men Project study, a large population-based epidemiological study of healthy ageing based in Sydney, Australia. We hypothesised that worry about health would be associated with having persistent pain, and that the association would be stronger in the presence of co-existing pain-related interference with activities (intrusive pain). Of men in the study, 12.5% had persistent and intrusive pain, 22.4% were worried about their health, and 6.3% had anxiety. We found a strong association between worry about health and pain that was both persistent and intrusive, and that remained after accounting for age, number of comorbidities, depression, self-rated health status, arthritis, and gait speed (adjusted odds ratio 2.9; 95% confidence interval 1.8-4.7), P<0.0001). The corresponding adjusted odds ratio for the association between anxiety and pain was 2.3 (95% confidence interval 1.0-4.8; P=0.0363). These findings suggest that at a population level, subthreshold anxiety and pain are strongly related, and worry about health occurs much more commonly than anxiety itself. To our knowledge, this is the first study to explore, specifically, the relationship between pain status and worry about health in older men. In older community-dwelling men, pain was robustly associated with worry about health, highlighting the potential importance of subthreshold anxiety-related psychological factors.

Socioeconomic status and bone health in community-dwelling older men: the CHAMP Study.

SUMMARY: The association between socioeconomic status (SES) and bone health, specifically in men, is unclear. Based upon data from the large prospective Concord Health in Ageing Men Project (CHAMP) Study of community-dwelling men aged 70 years or over, we found that specific sub-characteristics of SES, namely, marital status, living circumstances, and acculturation, reflected bone health in older Australian men. INTRODUCTION: Previous studies reported conflicting results regarding the relationship between SES and bone health, specifically in men. The main objective of this study was to investigate associations of SES with bone health in community-dwelling men aged 70 years or over who participated in the baseline phase of the CHAMP Study in Sydney, Australia. METHODS: The Australian Socioeconomic Index 2006 (AUSEI06) based on the Australian and New Zealand Standard Classification of Occupations was used to determine SES in 1,705 men. Bone mineral density and bone mineral content (BMC) were determined by dual-energy X-ray absorptiometry. Bone-related biochemical and hormonal parameters, including markers of bone turnover, parathyroid hormone, and vitamin D, were measured in all men. RESULTS: General linear models adjusted for age, weight, height, and bone area revealed no significant differences across crude AUSEI06 score quintiles for BMC at any skeletal site or for any of the bone-related biochemical measures. However, multivariate regression models revealed that in Australian-born men, marital status was a predictor of higher lumbar BMC (ß = 0.07, p = 0.002), higher total body BMC (ß = 0.05, p = 0.03), and lower urinary NTX-I levels (ß=-0.08, p = 0.03), while living alone was associated with lower BMC at the lumbar spine (ß=-0.05, p = 0.04) and higher urinary NTX-I levels (ß=0.07, p = 0.04). Marital status was also a predictor of higher total body BMC (ß = 0.14, p = 0.003) in immigrants from Eastern and South Eastern Europe. However, in immigrants from Southern Europe, living alone and acculturation were predictors of higher femoral neck BMC (ß = 0.11, p = 0.03) and lumbar spine BMC (ß = 0.10, p = 0.008), respectively. CONCLUSIONS: Although crude occupation-based SES scores were not significantly associated with bone health in older Australian men, specific sub-characteristics of SES, namely, marital status, living circumstances, and acculturation, were predictors of bone health in both Australia-born men and European immigrants.

Oral bisphosphonates are associated with reduced mortality in frail older people: a prospective five-year study.

UNLABELLED: In a study of 2005 institutionalized older people, use of oral bisphosphonates was associated with a 27% reduction in risk of death compared to non-users after adjusting for potential confounders. INTRODUCTION: This study investigated whether reductions in mortality reported in a trial of intravenous zoledronate after hip fracture could be seen in older people taking oral bisphosphonates. METHODS: Two thousand and five institutionalized older people (mean age 85.7 years) were assessed at baseline and followed up for hip fracture and death for at least 5 years. Cox proportional hazards regression was used to estimate effects of bisphosphonates on risk of death. RESULTS: At baseline, 78 subjects were taking oral bisphosphonates. Over 5 years of follow-up, 1,596 participants (80%) died. Use of bisphosphonates was associated with a 27% reduction in risk of death compared to non-users after adjusting for age, gender, type of institution, immobility, number of medications, weight, cognitive function, co-morbidities, and hip fracture incidence during the follow-up period (hazard ratio 0.73; 95% CI, 0.56 to 0.94; P = 0.02). CONCLUSION: Oral bisphosphonates are associated with a reduction in the risk of death in the elderly. The mechanism of effect requires further investigation.

Lifestyle factors, medications, and disease influence bone mineral density in older men: findings from the CHAMP study.

UNLABELLED: Aging alone is not the only factor accounting for poor bone health in older men. There are modifiable factors and lifestyle choices that may influence bone health and result in higher bone density and lower fracture risk even in very old men. INTRODUCTION: The aim of this cross-sectional analysis was to identify the factors associated with areal bone mineral density (BMD) and their relative contribution in older men. METHODS: The Concord Health and Ageing in Men Project is a population-based study in Sydney, Australia, involving 1,705 men aged 70-97. Data were collected using questionnaires and clinical assessments. BMD of the hip and spine was measured by dual X-ray absorptiometry. RESULTS: In multivariate regression models, BMD of the hip was associated with body weight and bone loading physical activities, but not independently with age. The positive relationship between higher BMD and recreational activities is attenuated with age. Factors independently associated with lower BMD at the hip were inability to stand from sitting, a history of kidney stones, thyroxine use, and Asian birth and at the spine, chronic obstructive pulmonary disease, paternal fracture history, and thyroxine use. Higher body weight, participation in dancing, tennis or jogging, quadriceps strength, alcohol consumption, and statin use were associated with higher hip BMD, while older age, osteoarthritis, higher body weight, and aspirin use were associated with higher spinal BMD. CONCLUSION: Maintaining body weight, physical activity, and strength were positively associated with BMD even in very elderly men. Other parameters were also found to influence BMD, and once these were included in multivariate analysis, age was no longer associated with BMD. This suggests that age-related diseases, lifestyle choices, and medications influence BMD rather than age per se.

Secondary osteoporosis in patients with an osteoporotic fracture.

Secondary osteoporosis is a common cause of osteoporosis, and there are many medical conditions associated with osteoporosis. Many of these present well before osteoporosis develops, and knowledge of these pre-existing conditions may influence the decision about whether to test and/or treat for osteoporosis. Men and premenopausal women with unexplained osteoporosis or a history of fragility fracture should undergo investigation for secondary osteoporosis. Postmenopausal women with risk factors for secondary osteoporosis should also be carefully evaluated. Beyond the well-recognised association with glucocorticoids, an increasing list of drugs has been implicated in causing bone loss and fractures. With appropriate consideration of secondary causes and relevant investigations, many of these conditions are preventable with newer therapies.

Efficacy, safety and patient-reported outcomes of combination etanercept and sulfasalazine versus etanercept alone in patients with rheumatoid arthritis: a double-blind randomised 2-year study.

OBJECTIVE: To determine the efficacy and safety of etanercept and etanercept plus sulfasalazine versus sulfasalazine in patients with rheumatoid arthritis (RA) despite sulfasalazine therapy. METHODS: Patients were randomly assigned to etanercept (25 mg twice weekly; sulfasalazine was discontinued at baseline), etanercept plus sulfasalazine (unchanged regimen of 2-3 g/day) or sulfasalazine in a double-blind, randomised, 2-year study in adult patients with active RA despite sulfasalazine therapy. Efficacy was assessed using the American College of Rheumatology criteria, disease activity scores (DAS) and patient-reported outcomes (PRO). RESULTS: Demographic variables and baseline disease characteristics were comparable among treatment groups; mean DAS 5.1, 5.2 and 5.1 for etanercept (n = 103), etanercept plus sulfasalazine (n = 101) and sulfasalazine (n = 50), respectively. Withdrawal due to lack of efficacy was highest with sulfasalazine (26 (52%) vs 6 (6%) for either etanercept group, p<0.001). Patients receiving etanercept or etanercept plus sulfasalazine had a more rapid initial response, which was sustained at 2 years, than those receiving sulfasalazine: mean DAS 2.8, 2.5 versus 4.5, respectively (p<0.05); ACR 20 response was achieved by 67%, 77% versus 34% of patients, respectively (p<0.01) Overall, PRO followed a similar pattern; a clinically significant improvement in health assessment questionnaire was achieved by 76%, 78% versus 40% of patients, respectively (p<0.01). Commonly reported adverse events occurring in the etanercept groups were injection site reactions and pharyngitis/laryngitis (p<0.01). CONCLUSION: Etanercept and etanercept plus sulfasalazine are efficacious for the long-term management of patients with RA. The addition of etanercept or substitution with etanercept should be considered as treatment options for patients not adequately responding to sulfasalazine.

Management of osteoporosis in primary care in Australia.

UNLABELLED: This study reviewed factors influencing osteoporosis management in primary care settings in Australia and examined risk profiles of patients (n = 37,957) for osteoporosis. Only 29.7% of patients with a prior fracture were currently on specific medication for osteoporosis. The results highlight the need for further exploration of barriers to osteoporosis management. INTRODUCTION: Osteoporosis management in primary care is suboptimal even for high-risk people with a history of prior fracture. METHODS: This study reviewed factors influencing the management of individuals at risk for osteoporosis in primary care settings in Australia and examined risk profiles of patients for osteoporosis. Patients (n = 37,957, mean age 71) were recruited over a 12-month period (February 2006-Jan 2007) and interviewed. RESULTS: With regard to risk factors for osteoporosis, 12.6% of patients reported a history of prior minimal trauma fracture, 7.5% reported a family history of osteoporosis, 7.4% reported they were current smokers, 11.4% reported low dietary calcium intake, 31.8% reported no regular weekly physical exercise and 10.3% reported current use of glucocorticoids. Of those with a prior fracture, only 29.7% were currently on specific medication for osteoporosis. Radiography (n = 17,754) demonstrated a prior vertebral fracture in 30.1%, but only 3.8% of the 17,754 patients reported current use of specific osteoporosis medication. CONCLUSIONS: This study has confirmed low rates of treatment in primary care even in individuals who have already suffered a prior fracture or have other risk factors. This study highlights the need for further exploration of barriers to osteoporosis management in the primary care setting.

Ibandronate for the prevention of nonvertebral fractures: a pooled analysis of individual patient data.

UNLABELLED: This analysis was conducted to assess the effect of high versus lower doses of ibandronate on nonvertebral fractures. The results were adjusted for clinical fracture, age, and bone density. The treatment effect was dose-dependent. Higher doses of ibandronate significantly reduced the risk of nonvertebral fractures more effectively compared with lower doses. INTRODUCTION: The objective of this study was to assess the efficacy of different doses of ibandronate on nonvertebral fractures in a pooled analysis. METHODS: Eight randomized trials of ibandronate were reviewed for inclusion. Alternative definitions of high versus low doses based on annual cumulative exposure (ACE) were explored. A time-to-event analysis was conducted using Kaplan-Meier methodology. Hazard ratios (HR) were derived using Cox regression and adjusted for covariates. RESULTS: Combining higher ACE doses of > or = 10.8 mg (150 mg once monthly, 3 mg i.v. quarterly, and 2 mg i.v. every 2 months) versus ACE doses of 5.5 mg, from two trials, resulted in an HR 0.62 (95% CI 0.396-0.974, p = 0.038). There was a dose-response trend with increasing ACE doses (7.2-12 mg) versus ACE of 5.5 mg. CONCLUSIONS: A dose-response effect on nonvertebral fractures was observed when comparing high with low ACE doses. A significant reduction in nonvertebral fractures was noted when pooling data from trials using ACE doses of > or = 10.8 mg versus ACE < or = 7.2 mg; and with ACE > or = 10.8 mg versus ACE of 5.5 mg (38% reduction). Higher ibandronate dose levels (150 mg monthly or 3 mg i.v. quarterly) significantly reduced nonvertebral fracture risk in postmenopausal women.