Effects of inflammation and treatment on bone turnover and bone mass in polymyalgia rheumatica

Abstract

Objective. Polymyalgia rheumatica (PMR) has an abrupt onset of inflammatory symptoms, making it a useful model for studying the effects of inflammation in bone. PMR requires corticosteroid treatment, which may itself have a detrimental effect on bone. This study used serially measured biochemical markers of bone turnover and bone density to address the relative contributions of systemic inflammation and corticosteroid therapy to bone loss.Methods. Fifty untreated patients with PMR were randomized to receive oral prednisolone or intramuscular methylprednisolone. Biochemical bone markers (pyridinoline [PYR] , deoxypyridinoline [DPYR] , procollagen type I carboxy-terminal peptide [PICP]) and bone mineral density (BMD) were measured at baseline and at 6, 12, and 24 months.Results. The median disease duration at presentation was 12 weeks (range 5-32 weeks). Levels of urinary crosslinks were increased in patients with untreated PMR compared with controls (PYR 74.9 f 30.0 nmoledmmole creatinine, DPYR 14.6 2 6.4 nmoles/ mmole creatinine [mean f SD]; P = 0.0001); the PICP level was normal (115.0 2 39.0 pg/liter). With treatment, the crosslinks levels fell and PICP levels rose within 6 months (P = 0.01). Bone resorption (PYR) correlated with untreated disease activity (erythrocyte sedimentation rate [ESR]) (r = 0.5, P = 0.003) and with interleukin-6 levels (r = 0.48, P = 0.05). There was Conclusion. Inflammation in PMR increases bone resorption and appears to have a more detrimental effect on bone than does low-dose corticosteroid. If corticosteroids can be tapered and discontinued, bone loss in PMR can be a transient phenomenon.

2015 Recommendations for the Management of Polymyalgia Rheumatica: A European League Against Rheumatism/American College of Rheumatology Collaborative Initiative

“…Baseline factors that were associated in low to moderate quality studies with a higher relapse rate and/or prolonged therapy in PMR studies were: female sex (24,26), high ESR (.40 mm/hour) (26)(27)(28)(29)(30)(31) and peripheral inflammatory arthritis (32). A number of equally low to moderate quality studies, however, failed to demonstrate an association between these factors and relapse/prolonged therapy (27)(28)(29)(30)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44). C. Consideration of specialist referral, particularly in case of atypical presentation (such as peripheral inflammatory arthritis, systemic symptoms, low inflammatory markers, age ,60 years), experience of or high risk of therapy-related side effects, PMR refractory to GC therapy, and/or relapses/prolonged therapy.…”

“…In clinical practice, MTX may be considered for example in female patients (36,39,47) with high initial erythrocyte sedimentation rate (ESR) (.40 mm/hour) (48-53), peripheral inflammatory arthritis (54) and/or comorbidities that may be exacerbated by GC therapy.…”

Bone loss in patients treated with pulses of methylprednisolone is not negligible: a short term prospective observational study

“…[24][25][26] In a longitudinal study a significant reduction in BMD was seen during the first 12 months, whereas BMD increased in the subsequent 12 months as the steroid dose was reduced. 25 In a cross sectional study no permanent reduction in BMD was seen in patients with polymyalgia rheumatica and temporal arteritis using daily oral low dose CS compared with controls. 26 Furthermore, in Cushing's syndrome a 20% bone loss has been shown to recover after successful treatment.…”

The Epidemiology of Corticosteroid-Induced Osteoporosis: a Meta-analysis

“…Figure 4 shows the bone loss from the spine of first-time user followed in longitudinal studies [9,20,25,33,38,42,51,56,67,71]. One limitation of evaluating bone loss longitudinally is that daily dose may vary and reduce over time.…”