Determinants of skeletal fragility in acromegaly: a systematic review and meta-analysis

Vertebral fractures (VFs) are a potential complication in acromegaly. However, the etiology of this skeletal fragility is unknown. This review aimed to evaluate the effect of acromegaly on VFs, bone turnover, areal bone mineral density (aBMD), and bone quality/microarchitecture. The effect of disease activity and gonadal status in these determinants of skeletal fragility was also evaluated.

Articles published in English until September 6, 2020 on PubMed and Embase that reported at least one determinant of skeletal fragility in acromegalic patients, were included. Odds ratio (OR) to evaluate the risk of VFs and the standardized mean difference (SMD) to evaluate bone turnover, aBMD and bone quality/microarchitecture were calculated.

Fifty-eight studies met eligibility criteria, assembling a total of 2412 acromegalic patients. Of these, 49 studies were included in the meta-analysis. Acromegalic patients, when compared to non-acromegalic patients, had higher risk of VFs [OR 7.00; 95% confidence interval (CI) 2.80-17.52; p < 0.0001], higher bone formation (SMD 1.14; 95% CI 0.69-1.59; p < 0.00001), higher bone resorption (SMD 0.60; 95% CI 0.09-1.10; p = 0.02) and higher aBMD at the femoral neck (SMD 0.36; 95% CI 0.15-0.57; p = 0.0009). No significant differences were found regarding aBMD at lumbar spine. Considering the results of the different techniques evaluating bone quality/microarchitecture, the main reported alterations were a decrease in trabecular bone thickness and density, and an increase in trabecular separation. The presence of active disease and/or hypogonadism were associated with worst results.

Patients with acromegaly are at increased risk of VFs, mainly because of deterioration in bone microarchitecture.