No abstract

Objective: Arthropathy is an invalidating complication of acromegaly, of which the prognosis and determinants are currently unknown in treated acromegaly. Therefore, the objective of the present study was to investigate the radiographic progression of arthropathy over a mean follow-up period of 2.6 years and determinants of outcome in patients with long-term, well-controlled acromegaly. Design: Prospective follow-up study. Methods: In a prospective cohort study we studied 58 patients (mean age 62, women 41%) with controlled acromegaly for a mean of 17.6 years. Radiographic progression of joint disease was defined by the Osteoarthritis Research Society International classification as a 1-point increase in joint space narrowing (JSN) or osteophyte scores on radiographs of the hands, knees, and hips obtained at the first study visit and after 2.6 years. Potential risk factors for progression were assessed. Results: Progression of osteophytes and JSN was observed in 72 and 74% of patients respectively. Higher age predisposed for osteophyte progression. Patients with biochemical control by somatostatin (SMS) analogs had more progression of osteophytosis than surgically cured patients (odds ratioZ18.9, PZ0.025), independent of age, sex, BMI, baseline IGF1 SDS and exon 3 deletion of the GHR. This was also evident for JSN progression, as were higher age and higher baseline IGF1 SDS. Conclusions: Acromegalic patients have progressive JSN and osteophytosis, despite long-term biochemical control. Parameters reflecting GH/IGF1 activity were associated with progressive joint disease. Remarkably, biochemical control by SMS analogs was associated with more progression than surgical cure. Although the present study is not a randomized controlled trial, this may indicate insufficient GH control according to current criteria and the need for more aggressive therapy.

Arthropathy is an invalidating complication of acromegaly. This arthropathy deteriorates radiographically despite long-term disease control. However, the clinical course and its relationship to the radiographic course are currently unknown. We aimed to investigate the clinical course of arthropathy during follow-up and its relationship to radiographic progression in long-term controlled acromegaly patients. Prospective follow-up study. We studied 58 patients (mean age 62 years, women 41 %) with controlled acromegaly for a mean of 17.6 years. Clinical progression of joint disease was defined at baseline and after 2.6 years, by the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) and Australian/Canadian Osteoarthritis Index (AUSCAN) questionnaires for lower limb and hand OA, respectively, and performance tests. Potential risk factors for progression were assessed. The clinical course of arthropathy was related to the radiographic course. On average, hand and lower limb function deteriorated during follow-up, despite large interindividual variations. Joint pain was stable over time. High levels of pain and functional impairment at baseline were related to clinical progression of hand pain and functional limitations. High baseline BMI was a risk factor for functional deterioration in the lower limb. The changes in symptoms and radiographic progression during follow-up were not related. In treated acromegaly patients, joint function deteriorates during prolonged follow-up, despite biochemical disease control, although there was interindividual variation. Clinical and radiographic course of arthropathy were not related. Therefore, in clinical practice, a combination of clinical and radiographic assessment is necessary to evaluate the course of acromegalic arthropathy.

Observational data showed no association between serum IGF-1 and occurrence of radiographic OA (moderate level of evidence), and a positive relationship between IGF-1 gene polymorphisms and radiographic OA (moderate level of evidence); however the confounding effect of BMI was insufficiently addressed. Future well-designed prospective studies should further elaborate the role of the complex GH/IGF-1 system in primary OA.

Atypical fractures of the femur have been reported to occur in patients on long-term treatment with bisphosphonates; however, causality has not been proven, and it is not known whether similar fractures may occur in other long bones. We addressed this issue by examining the relationship between humeral shaft fractures and bisphosphonate use. We identified all patients aged !50 years consecutively admitted to a single center with a new fracture of the humerus. All individual radiographs were examined and fracture site was classified. A case-control study was undertaken in patients with humeral shaft fractures, and controls were sex-and age-matched patients with proximal humeral fractures in a 1:4 ratio. Patients with shaft fractures and radiographic characteristics similar to those of atypical femoral fractures were compared with those with ordinary shaft fractures. The association between ''atypical'' fractures and bisphosphonate or glucocorticoid use was examined. A total of 198 patients had a low-energy fracture of the humerus; 20 of these patients had a shaft fracture (10%). These 20 patients (cases) were matched with 80 patients with proximal fractures (controls). Bisphosphonates were used by 5% of cases and by 6.3% of controls (odds ratio [OR], 0.80; 95% confidence interval [CI], 0.09-6.85); glucocorticoids were used by 10% of cases and 8.8% of controls (OR, 1.15; 95% CI, 0.23-5.83). There was no difference in cortical thickness between cases and controls and bisphosphonate or glucocorticoid users and nonusers. Four of the 20 patients with shaft fractures had ''atypical'' radiographic features, with significantly increased cortical thickness, but none of these had ever been treated with bisphosphonates or glucocorticoids. Our results show that low-energy fractures of the humeral shaft with ''atypical'' radiographic characteristics are infrequent and are not associated with the use of bisphosphonates or glucocorticoids. ß