Long-term pegvisomant therapy of acromegaly: Effects on bone density, turnover and microstructure using HRpQCT
Adriana P Kuker, Sanchita Agarwal, Elizabeth Shane, Juliana Bicca, Eliza B Geer, Serge Cremers, Elzbieta Dworakowski, Adi Cohen, Thomas L Nickolas, Emily M Stein, Pamela U Freda- Endocrinology, Diabetes and Metabolism
Abstract
Context
Fracture rate is increased in patients with active acromegaly and those in remission. Abnormalities of bone microstructure are present in patients with active disease and persist despite biochemical control after surgery. Effects of treatment with the GH receptor antagonist pegvisomant on bone microstructure were unknown.
Methods
We studied 25 patients with acromegaly (15 men, 10 women). In 20, we evaluated arealBMD by DXA and bone turnover markers (BTMs) longitudinally, before and during pegvisomant treatment. After long-term pegvisomant in 17, we cross-sectionally assessed volumetric BMD, microarchitecture, stiffness and failure load of the distal radius and tibia using HRpQCT and compared these results to those of healthy controls and 2 comparison groups of non-pegvisomant treated acromegaly patients, remission and active disease, matched for other therapies and characteristics.
Results
In the longitudinal study, aBMD improved at the LS, but decreased at the hip in men after a median ∼7 years of pegvisomant. In the cross-sectional study, patients on a median ∼9 years of pegvisomant had significantly larger bones, lower trabecular and cortical volumetric density and disrupted trabecular microarchitecture compared to healthy controls. Microstructure was similar in the pegvisomant and acromegaly comparison groups. BTMs were lowered, then stable over time.
Conclusions
In this, the first study to examine bone microstructure in pegvisomant-treated acromegaly, we found deficits in volumetric BMD and microarchitecture of the peripheral skeleton. BTM levels remained stable with long-term therapy. Deficits in bone quality identified by HRpQCT may play a role in the pathogenesis of fragility in treated acromegaly.