One-year effects of glucocorticoids on bone density: a meta-analysis in cohorts on high and low-dose therapy.

BACKGROUND: Bone loss during glucocorticoid (GC) therapy is poorly quantified. OBJECTIVE: Quantification of bone loss in GC-treated patients with chronic inflammatory diseases (CID; low dose) and transplants (high dose). METHODS: Meta-analysis of cohorts: PubMed, Cochrane, EMBASE and bibliographic searches (1995-2012). Eligible studies prospectively included GC-treated patients with two dual X-ray absorptiometry measurements of spine or hip over a period of at least 12 months. Only supplementation with calcium or vitamin D3 was allowed. 5602 titles yielded 285 articles: 51 study arms in CID (N=1565), 18 study arms in transplantation (N=571). Prednisone-equivalent GC doses and inverse variance weighted mean bone changes were used in a random effects model. RESULTS: In CID, the mean GC dose was 8.7 mg/day (range 1.2-16.4). The mean 1-year bone loss in the lumbar spine was -1.7% (95% CI -2.2% to -1.2%); in the femoral neck: -1.3 (-1.8 to -0.7). In transplantation, the mean GC dose was 18.9 mg/day (range 6.0-52.7). Bone loss in the lumbar spine was -3.6% (-5.2% to -2.0%); in the femoral neck: -3.1% (-5.1% to -1.1%). Within the two groups, bone loss was not related to GC dose. CONCLUSION: In CID, GC-related bone loss appears limited and manageable if current anti-osteoporotic strategies are fully implemented. In transplantation, and probably also other high-dose settings, bone loss is considerable and represents unmet need. The heterogeneity probably reflects the important influence of other factors, most notably the underlying disease and the efficacy of GC treatment.

Short term whole body retention in relation to rate of bone resorption and cartilage degradation after intravenous bisphosphonate (pamidronate) in rheumatoid arthritis.

OBJECTIVE: Bisphosphonates (BP) inhibit osteoclast-mediated bone resorption, and have been reported to decrease the rate of cartilage degradation. The anti-resorptive effect of BP is determined by the amount of BP retained by the skeleton. In rheumatoid arthritis (RA) the uptake is not confined only to the skeleton, but BP is also retained in joints, which could have implications for dose regimens. We investigated the whole body retention (WBR) of pamidronate and its relationship to bone resorption and cartilage degradation in patients with active RA. METHODS: Twenty-six patients received placebo, 45 mg, or 90 mg intravenous pamidronate. Serum and urine samples were collected before and for 12 days after drug administration. Rate of bone resorption was assessed by the biochemical markers: serum carboxy terminal cross-linked telopeptide of type I collagen, urinary carboxy terminal cross-linked telopeptide of type I collagen normalized to creatinine and urinary amino-terminal telopeptide of type I collagen normalized to creatinine; and rate of cartilage degradation by urinary carboxy terminal telopeptide of type II collagen normalized to creatinine. WBR was derived from urinary excretion of pamidronate data. RESULTS: Pamidronate induced a rapid and sustained decrease in the level of biochemical markers of bone resorption and cartilage degradation. The mean WBR of pamidronate was 69% of the administered dose, and showed a remarkably wide range (41-96%). The decrease in rate of bone resorption, but also rate of cartilage degradation appeared to be related to the WBR of pamidronate. CONCLUSION: This is the first study in which the effect of BP treatment has been studied in relation to the amount of BP retained by the body in patients with active RA. The total amount of BP retained by the body shows a remarkably wide range and is comparable with literature on patients with osteoporosis. The apparent relationships between the amount of BP retained by the body and the effect could have implications for therapeutic regimens in patients with RA.

Radiographic damage associated with low bone mineral density and vertebral deformities in rheumatoid arthritis: the Oslo-Truro-Amsterdam (OSTRA) collaborative study.

OBJECTIVE: To examine variables associated with bone mineral density (BMD) and vertebral deformities in women with rheumatoid arthritis (RA) from 3 northwest European countries. METHODS: Female patients were recruited from rheumatology clinics in Oslo, Norway; Truro, UK; and Amsterdam, The Netherlands (150 total, 50 per center, age 50-70 years, disease duration > or = 5 years). Demographic and clinical data were collected and BMD was measured by means of dual energy x-ray absorptiometry. Associations between demographic and clinical measures on the one hand and BMD and vertebral deformities on the other were investigated by single and multiple regression analyses. RESULTS: Body mass index (BMI), medication use, RA damage measures, and BMD differed significantly between the 3 centers. Overall, Norwegian patients had the lowest BMI, used more corticosteroids and anti-osteoporotic drugs, had lower joint damage measured by Larsen score, and lower BMD at both spine and hip. High age, low BMI, and high cumulative dose of corticosteroids (last 2 years) are related to low BMD. A high Larsen score was associated with low BMD at the hip. Larsen score was the independent determinant of vertebral deformities after correction for center, age, BMI, and BMD. CONCLUSION: Data from 3 countries on BMD and vertebral deformities in female patients aged 50-70 years with longstanding RA are presented, demonstrating an association between radiographic RA damage and low BMD and between radiographic RA damage and vertebral deformities.