THE DELETERIOUS EFFECTS OF LOW-DOSE CORTICOSTEROIDS ON BONE-DENSITY IN PATIENTS WITH POLYMYALGIA-RHEUMATICA

The beneficial effects of corticosteroid therapy in the treatment of r heumatic diseases may be offset by the occurrence of corticosteroid-re lated osteoporosis. This problem may be overcome by using low-dose cor ticosteroids; however, the dose of corticosteroids that is both effica cious and skeletal sparing is uncertain. Therefore, the aim of this st udy was to determine whether low-dose prednisolone treatment results i n bone loss and modifies bone turnover. Nineteen patients (12 female, seven male) suffering from polymyalgia rheumatica received 10 mg or le ss daily, given in reducing dosage, with a range of 2.5-10 mg and an a verage of 6.0 +/- 0.2 mg daily (+/-S.E.M.). Prior to the commencement of therapy and at regular intervals during treatment, bone mineral den sity (BMD) using dual X-ray absorptiometry and circulating biochemical and hormonal determinants of bone turnover were measured. The patient s were followed for 14.4 +/- 1.6 months (range 6-27). They were compar ed to 19 age-matched controls. Despite a mean exposure dose of 6 mg/da y and disease remission, BMD decreased in the patients at the lumbar s pine (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 f irst 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 decre ased at the lumbar spine (1.7 +/- 0.9%, P = 0.06). From 6 months to th e 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 no t suppressed by disease before treatment, decreased by 27.4 +/- 5.1% d uring the first month of treatment (P < 0.001), remained suppressed wh ile the daily dose of prednisolone was >5 mg/day, but returned to base line 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 inc reased by 20-60% (P < 0.05 to < 0.01). Prophylaxis should be considere d in patients receiving greater than or equal to 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 bo ne loss may predispose to hip fractures. Doses of prednisolone of <5 m g daily may be skeletal sparing, but may not be efficacious.