title: The deleterious effects of low-dose corticosteroids on bone density in patients with polymyalgia rheumatica.
abstract: The beneficial effects of corticosteroid therapy in the treatment of rheumatic diseases may be offset by the occurrence of corticosteroid-related osteoporosis. This problem may be overcome by using low-dose corticosteroids; however, the dose of corticosteroids that is both efficacious and skeletal sparing is uncertain. Therefore, the aim of this study was to determine whether low-dose prednisolone treatment results in bone loss and modifies bone turnover. Nineteen patients (12 female, seven male) suffering from polymyalgia rheumatica received 10 mg or less daily, given in reducing dosage, with a range of 2.5-10 mg and an average of 6.0+/-0.2 mg daily (+/-S.E.M.). Prior to the commencement of therapy and at regular intervals during treatment, bone mineral density (BMD) using dual X-ray absorptiometry and circulating biochemical and hormonal determinants of bone turnover were measured. The patients were followed for 14.4+/-1.6 months (range 6-27). They were compared to 19 age-matched controls. Despite a mean exposure dose of 6 mg/day and disease remission, BMD decreased in the patients at the lumbar spine (2.6+/-0.8%, P < 0.01), femoral neck (2.9+/-1.5%, P=0.06), Ward's triangle (5.5+/-2.9%, P=0.06) and the trochanter (4.3+/-1.9%, P < 0.05). Total body bone mass decreased by 50+/-19 g in the first 6 months (P < 0.02), and by 39+/-30 g in the remaining 8 months of follow-up [not significant (NS)]. In the first 6 months, BMD decreased at the lumbar spine (1.7+/-0.9%, P = 0.06). From 6 months to the end of follow-up, BMD decreased by 8.5+/-3.5% at Ward's triangle (P < 0.05) and by 4.8+/-2.5% at the femoral neck (P=0.08). The fall in BMD correlated with the cumulative prednisolone dose at trabecular-rich regions (trunk r=-0.72, P < 0.001; ribs r=-0.53, P < 0.05). Bone resorption, assessed by urinary cross-laps, was 54.7% higher than controls before treatment was started (P < 0.05) and decreased by 23.5+/-7.1% in the first month of treatment when the mean prednisolone dose was 9.1 mg/day, range 5-10 (P < 0.0001). Serum osteocalcin was not suppressed by disease before treatment, decreased by 27.4+/-5.1% during the first month of treatment (P < 0.001), remained suppressed while the daily dose of prednisolone was > 5 mg/day, but returned to baseline below this dose. Serum parathyroid hormone was 19.3% lower in the patients than controls at baseline (NS), and increased by 46.1% (P < 0.05) but was no higher than controls at any time. Muscle strength increased by 20-60% (P < 0.05 to < 0.01). Prophylaxis should be considered in patients receiving > or = 5 mg/day prednisolone daily as bone loss is 2- to 3-fold expected rates. Earlier trabecular bone loss may predispose to spine and rib fracture; later cortical bone loss may predispose to hip fractures. Doses of prednisolone of < 5 mg daily may be skeletal sparing, but may not be efficacious.
authors.affiliation: Austin and Repatriation Medical Centre, Heidelberg, Victoria, Australia.
authors.forename: G
authors.initials: G
authors.lastname: Pearce
authors.forename: P F
authors.initials: PF
authors.lastname: Ryan
authors.forename: P D
authors.initials: PD
authors.lastname: Delmas
authors.forename: D A
authors.initials: DA
authors.lastname: Tabensky
authors.forename: E
authors.initials: E
authors.lastname: Seeman
mesh_terms: D000368:Aged; D000469:Alkaline Phosphatase / Q000032:analysis; D000735:Androstenedione / Q000097:blood; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000201:enzymology; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D015675:Osteocalcin / Q000097:blood; D010024:Osteoporosis / Q000139:chemically induced*; D015663:Osteoporosis, Postmenopausal / Q000139:chemically induced / Q000503:physiopathology; D011111:Polymyalgia Rheumatica / Q000097:blood / Q000188:drug therapy*; D011239:Prednisolone / Q000008:administration & dosage / Q000009:adverse effects*; D011446:Prospective Studies
chemical_list: D000893:Anti-Inflammatory Agents; D015675:Osteocalcin; D019382:Human Growth Hormone; D000735:Androstenedione; D019314:Dehydroepiandrosterone Sulfate; D007334:Insulin-Like Growth Factor I; D011239:Prednisolone; D000469:Alkaline Phosphatase