SAT-438 Visceral and Marrow Adiposity in Patients with Acromegaly; Relationships to Disease Activity, Markers of Bone Turnover, Bone Mineral Density, and Peripheral Bone Microarchitecture

Abstract

Adipose tissue (AT) mass, especially visceral (VAT), is reduced in active acromegaly and rises with treatment. Although the effect of acromegaly and its therapy on marrow AT(MAT) is unknown, data in other populations and in vitro, suggest a reciprocal relationship between GH and marrow adiposity. In other groups, VAT and MAT are associated with reduced bone quality and increased vertebral fracture (VF) risk. Therefore, since acromegaly patients have an increased VF incidence, we examined the relationships of VAT and MAT to bone quality in acromegaly. We studied 65 acromegaly subjects (40 men, 25 women, range 18.7-74 yr.) before (n=20) or before and after (n=45) acromegaly therapy by total body multi-slice MRI(n=159)(measurement of VAT, subcutaneous (SAT) and total (TAT) adipose tissue mass), DXA (BMD (n=120) and body composition (n=145)) and HRpQCT (n=35) (microarchitecture of the tibia and radius). Marrow lipid spectra of the tibial diaphysis were acquired by 1H MRS (PRESS technique)(1.5T MR scanner, Philips) and percentages of bone marrow lipids were quantified (n=53). GH and IGF-1 (n=159) and bone turnover markers (BTM)(n=49) were measured. We examined the relationship between MAT or VAT and GH, IGF-1, age, weight, mass of other MRI measured AT depots, and selected DXA and HRpQCT parameters previously shown to differ in acromegaly compared to healthy subjects and to be associated in other groups with fracture. Data were analyzed by Pearson correlation and the generalized estimating equation (GEE). MAT directly correlated with VAT (r=.249, p=.023) and by HRpQCT (n=13) with bone size (radius: total area (r=.678, p=.01), tibia: total area (r=.535, p=.05)) and trabecular number (r=.543, p=.055). VAT was inversely associated with GH (β= -.017, p<.001), IGF-1 level (expressed as % upper normal limit) (β= -0.004, p=.049) and BTMs (N-Mid Osteocalcin (β= -.0223, p<0.001); CTX (β= -.7283, p=.0134)). VAT was positively associated with age (β=.034, p=.053), weight (β=.072, p <.0001) and with HRpQCT measured bone size (radius: total area (β=.0073, p=.0098); tibia: total area (β= .0049, p <.0001)) and trabecular number (tibia: β=1.9321, p=.0096), and inversely associated with cortical thickness (radius: β= -2.8477, p= .074; tibia: β= -2.3341, p=.0497), trabecular thickness (tibia: β= -92, p<.0001) and total body density (radius β= -.0102, p=.0353; tibia: β= -.0149, p=.003). In summary, VAT is inversely related to acromegaly disease activity, consistent with its known rise as acromegaly is treated. We found that greater VAT is associated with larger bone size and lower bone turnover, but also with some less favorable aspects of bone microarchitecture. MAT correlated with VAT and, in a small number of subjects, with bone size. Whether rising adiposity and reductions in bone turnover with acromegaly therapy are relevant to the skeletal fragility reported in treated acromegaly warrants further study.