Association of plasma n-6 and n-3 polyunsaturated fatty acids with synovitis in the knee: the MOST study.

In osteoarthritis (OA) the synovium is often inflamed and inflammatory cytokines contribute to cartilage damage. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have anti-inflammatory effects whereas omega-6 polyunsaturated fatty acids (n-6 PUFAs) have, on balance, proinflammatory effects. The goal of our study was to assess the association of fasting plasma phospholipid n-6 and n-3 PUFAs with synovitis as measured by synovial thickening on contrast enhanced (CE) knee MRI and cartilage damage among subjects in the Multicenter Osteoarthritis Study (MOST). MOST is a cohort study of individuals who have or are at high risk of knee OA. An unselected subset of participants who volunteered obtained CE 1.5T MRI of one knee. Synovitis was scored in six compartments and a summary score was created. This subset also had fasting plasma, analyzed by gas chromatography for phospholipid fatty acid content, and non-CE MRI, read for cartilage morphology according to the Whole-Organ Magnetic Resonance Imaging Score (WORMS) method. The association between synovitis and cartilage morphology and plasma PUFAs was assessed using logistic regression after controlling for the effects of age, sex, and BMI. 472 out of 535 subjects with CE MRI had complete data on synovitis, cartilage morphology and plasma phospholipids. Mean age was 60 years, mean BMI 30, and 50% were women. We found an inverse relation between total n-3 PUFAs and the specific n-3, docosahexaenoic acid with patellofemoral cartilage loss, but not tibiofemoral cartilage loss or synovitis. A positive association was observed between the n-6 PUFA, arachidonic acid, and synovitis. In conclusion, systemic levels of n-3 and n-6 PUFAs which are influenced by diet, may be related to selected structural findings in knees with or at risk of OA. Future studies manipulating the systemic levels of these fatty acids may be warranted to determine the effects on structural damage in knee OA.

Higher 1,25-dihydroxyvitamin D3 concentrations associated with lower fall rates in older community-dwelling women.

INTRODUCTION: The purpose of this study was to examine the relationships of vitamin D supplementation and serum concentrations of vitamin D metabolites and parathyroid hormone (PTH) with neuromuscular function and falls in older community-dwelling women. METHODS: We examined these relationships using a 4-year prospective multi-center study among 9,526 community-dwelling women enrolled in the Study of Osteoporotic Fractures (median age: 70 years; interquartile range: 67-75) and a subset of 389 women (97%) out of 400 who were randomly selected from the entire cohort for serum measures. Measurements included: vitamin D supplementation, serum 25-hydroxyvitamin D(3) [25(OH)D(3)], serum 1,25-dihydroxyvitamin D(3) [1,25(OH) (2)D(3)], and serum intact parathyroid hormone (iPTH); grip and quadriceps strength, chair-stand time, walking speed, reaction time, and balance-walk time (including changes in grip strength, chair-stand time, walking speed and balance-walk time over approximately 3.7 years); and incident fall rates (number of falls/woman-years). RESULTS: In 9,526 women, vitamin D supplementation was not associated with any measures of neuromuscular function, change in neuromuscular function, or fall rates (p>0.01 for all). In a subgroup of 389 women, there was a trend of higher 25(OH)D(3) concentration with slightly weaker grip strength (p=0.007), and women in the fourth quartile of 1,25(OH)(2)D(3) had a faster chair-stand time (p=0.017) than women in the first quartile; still, in general, concentrations of 25(OH)D(3), 1,25(OH)(2)D(3), and iPTH were not associated with either neuromuscular function or changes in neuromuscular function (p>0.05 for all). However, higher 1,25(OH)(2)D(3) concentration was associated with lower fall rates (p=0.039). CONCLUSIONS: Higher 1,25(OH)(2)D(3) concentration is associated with a lower fall risk in older community-dwelling women, but vitamin D supplementation, and 25(OH)D(3) and iPTH concentrations are not associated with either neuromuscular function or falls.

Two-year effects of alendronate on bone mineral density and vertebral fracture in patients receiving glucocorticoids: a randomized, double-blind, placebo-controlled extension trial.

OBJECTIVE: To evaluate the continued efficacy and safety of alendronate (ALN) for up to 2 years in patients receiving glucocorticoids. METHODS: This is a 12-month extension of a previously completed 1-year trial of daily ALN, performed to evaluate the effects of ALN over a total of 2 years in 66 men and 142 women continuing to receive at least 7.5 mg of prednisone or equivalent daily. All patients received supplemental calcium and vitamin D. The primary end point was the mean percentage change in lumbar spine bone mineral density (BMD) from baseline to 24 months. Other outcomes included changes in hip and total body BMD, biochemical markers of bone turnover, radiographic joint damage of the hands, and vertebral fracture incidence. RESULTS: The mean (+/-SEM) lumbar spine BMD increased by 2.8 +/- 0.6%, 3.9 +/- 0.7%, and 3.7 +/- 0.6%, respectively, in the groups that received 5 mg, 10 mg, and 2.5/10 mg of ALN daily (P < or = 0.001) and decreased by -0.8 +/- 0.6% in the placebo group (P not significant) over 24 months. In patients receiving any dose of ALN, BMD was increased at the trochanter (P < or = 0.05) and maintained at the femoral neck. Total body BMD was increased in patients receiving 5 or 10 mg ALN (P < or = 0.01). These 2 dose levels of ALN were more effective than placebo at all sites (P < or = 0.05). Bone turnover markers (N-telopeptides of type I collagen and bone-specific alkaline phosphatase) decreased 60% and 25%, respectively, during treatment with ALN (P < or = 0.05). There were fewer patients with new vertebral fractures in the ALN group versus the placebo group (0.7% versus 6.8%; P = 0.026). The safety profile was similar between treatment groups. CONCLUSION: Alendronate is an effective, well-tolerated therapy for the prevention and treatment of glucocorticoid-induced osteoporosis, with sustained treatment advantages for up to 2 years.

Serum vitamin D levels and incident changes of radiographic hip osteoarthritis: a longitudinal study. Study of Osteoporotic Fractures Research Group.

OBJECTIVE: The purpose of this study was to determine the relationship of serum levels of 25-vitamin D and 1,25-vitamin D to incident changes of radiographic hip osteoarthritis (OA) among elderly white women. METHODS: Baseline and followup hip radiographs of 237 subjects were obtained an average of 8 years apart. Hips were scored for individual radiographic features (IRF) and assigned a summary grade based on the number and type of IRF present. Serum 25- and 1,25-vitamin D levels from baseline samples were analyzed by radioimmunoassay. Logistic and linear regression were used to examine the association of 25- and 1,25-vitamin D levels with radiographic changes, adjusting for age, health status, physical activity, weight, vitamin D supplement use, and calcaneal bone mineral density. RESULTS: The risk of incident hip OA defined as the development of definite joint space narrowing was increased for subjects who were in the middle (odds ratio [OR] 3.21, 95% confidence interval [95% CI] 1.06, 9.68) and lowest (OR 3.34, 95% CI 1.13, 9.86) tertiles for 25-vitamin D compared with subjects in the highest tertile. Vitamin D levels were not associated with incident hip OA defined as the development of definite osteophytes or new disease according to the summary grade. No association between serum 1,25-vitamin D and changes in radiographic hip OA was found. CONCLUSION: Low serum levels of 25-vitamin D may be associated with incident changes of radiographic hip OA characterized by joint space narrowing.

Depression, falls, and risk of fracture in older women. Study of Osteoporotic Fractures Research Group.

BACKGROUND: Previous studies have suggested that depression is associated with falls and with low bone density, but it is not known whether depression leads to an increased risk of fracture. SUBJECTS AND METHODS: We conducted a prospective cohort study in elderly white women who were recruited from population-based listings in the United States. At a second visit (1988-1990), 7414 participants completed the 15-item Geriatric Depression Scale and were considered depressed if they reported 6 or more symptoms of depression. We measured bone mineral density (BMD) in the spine and hip using dual energy x-ray absorptiometry at the second visit, and asked participants about incident falls (yes/no) at 4 follow-up visits. Nonvertebral fractures were ascertained for an average of 6 years following the depression measure, and verified radiologically. We determined incident vertebral fractures by comparing lateral spine films obtained at the first visit (1986-1988) with repeat films obtained an average of 3.7 years later (1991-1992). RESULTS: The prevalence of depression (Geriatric Depression Scale score > or = 6) was 6.3% (467/7414). We found no difference in mean BMD of the hip and lumbar spine in women with depression compared with those without depression. Women with depression were more likely to experience subsequent falls than women without depression (70% vs 59%; age-adjusted odds ratio [OR], 1.6; 95% confidence interval [CI], 1.3-1.9; P<.001), an association that persisted after adjusting for potential confounding variables (OR, 1.4; 95% CI, 1.1-1.8; P=.004). Women with depression had a 40% (age-adjusted hazard ratio [HR], 1.4; 95% CI, 1.2-1.7; P<.001) increased rate of nonvertebral fracture (124 fractures in 3805 woman-years of follow-up) compared with women without depression (1367 fractures in 59 503 woman-years of follow-up). This association remained strong after adjusting for potential confounding variables, including medication use and neuromuscular function (HR, 1.3; 95% CI, 1.1-1.6; P=.008). Further adjustment for subsequent falls appeared to explain part of this association (HR, 1.2; 95% CI, 1.0-1.5; P = .06). Women with depression were also more likely to suffer vertebral fractures than women without depression, adjusting for history of vertebral fracture, history of falling, arthritis, diabetes, steroid use, estrogen use, supplemental calcium use, cognitive function, and hip BMD (OR, 2.1; 95% CI, 1.4-3.2; P<.001). CONCLUSIONS: Depression is a significant risk factor for fracture in older women. The greater frequency of falls among individuals with depression partially explains this finding. Other mechanisms responsible for the association between depression and fracture remain to be determined.

Calcium for prevention of osteoporotic fractures in postmenopausal women.

A systematic review of the literature was conducted to assess the effectiveness of calcium supplements and/or dietary calcium for the prevention of osteoporotic fractures in postmenopausal women. Studies were identified by conducting a Medline search using the text words "fracture" and "calcium" for the period 1966 to March 1997 and by reviewing articles known to the authors. Only studies with fracture outcomes were eligible. There were 14 studies of calcium supplements (including 4 randomized trials), 18 studies of dietary calcium and hip fracture (no randomized trials), and 5 studies of dietary calcium and other fracture sites (no randomized trials). The 4 randomized trials of calcium supplements (mean calcium dose: 1050 mg) found relative risk (RR) reductions between 25% and 70%. Meta-analytic techniques for dose-response data were used to investigate and pool the findings of 16 observational studies of dietary calcium and hip fracture. These hip fracture studies were not consistent and heterogeneity of study findings (p = 0.02) was not easily explained by subject characteristics or study design. Pooling study results gave an odds ratio (OR) of 0.96 (95% confidence interval, (CI) 0.93-0.99) per 300 mg/day increase in calcium intake (the equivalent of one glass of milk). This is likely to be an underestimate of calcium's true effect because of inaccurate measurement of dietary calcium in observational studies. This review supports the current clinical and public health policy of recommending increased calcium intake among older women for fracture prevention.

Calcium intake and fracture risk: results from the study of osteoporotic fractures.

The relation between dietary calcium, calcium, and vitamin D supplements and the risk of fractures of the hip (n = 332), ankle (n = 210), proximal humerus (n = 241), wrist (n = 467), and vertebrae (n = 389) was investigated in a cohort study involving 9,704 US white women aged 65 years or older. Baseline assessments took place in 1986-1988 in four US metropolitan areas. Dietary calcium intake was assessed at baseline with a validated food frequency questionnaire. Data on new nonvertebral fractures were collected every 4 months during a mean of 6.6 years of follow-up; identification of new vertebral fractures was based on comparison of baseline and follow-up radiographs of the spine done a mean of 3.7 years apart. Results were adjusted for numerous potential confounders, including weight, physical activity, estrogen use, protein intake, and history of falls, osteoporosis, and fractures. There were no important associations between dietary calcium intake and the risk of any of the fractures studied. Current use of calcium supplements was associated with increased risk of hip (relative risk = 1.5, 95% confidence interval 1.1-2.0) and vertebral (relative risk = 1.4, 95% confidence interval 1.1-1.9) fractures; current use of Tums antacid tablets was associated with increased risk of fractures of the proximal humerus (relative risk = 1.7, 95% confidence interval 1.3-2.4). There was no evidence of a protective effect of vitamin D supplements. Although a true adverse effect of calcium supplements on fracture risk cannot be ruled out, it is more likely that our findings are due to inadequately controlled confounding by indications for use of supplements. In conclusion, this study did not find a substantial beneficial effect of calcium on fracture risk.