High prevalence of vertebral fractures despite normal bone mineral density in patients with long-term controlled acromegaly

Abstract

Objective: To establish the prevalence of osteoporosis, vertebral fractures (VFs), and non-VFs in acromegaly patients with long-term controlled disease and factors potentially influencing fracture risk. Design: Case-control study. Patients and measurements: Eighty-nine patients (46% male, mean age: 58 years) were included. We studied VFs and non-VFs, bone mineral density (BMD), and markers of bone turnover. In 48 patients, BMD assessment was also obtained 7 years prior to the current study. To compare VF prevalence, data from a sample of the Dutch population (nZ3469) were used. Results: VF prevalence was 59% (men 64% and women 54%), significantly increased when compared with controls (odds ratio up to 6.5), and independent of the duration of disease control, BMD, markers of bone turnover, and acromegalic disease characteristics. Mean number of VFs per patient was 3.4G0.3 (range 1-8). There was no relationship between the number and severity of fractures, parameters of bone turnover, and follow-up BMD measurements. BMD did not change during prolongation of follow-up by 7 years of controlled acromegaly. Conclusion: There is a very high prevalence of VFs in acromegaly patients with long-term controlled disease, independently of BMD. In view of the significant morbidity and mortality associated with VFs in general and the inability of BMD to predict fracture risk in acromegalic patients, we propose to include VF assessment, for example by lateral conventional radiographs of the spine in the screening of patients with acromegaly, both at diagnosis and during follow-up after establishment of disease control.

Treatment of acromegaly increases BMD but reduces trabecular bone score: a longitudinal study

“…It is therefore to be expected that disease control in acromegaly will be followed by a decrease in bone turnover and a filling of the remodeling space followed by a relative increase in BMD (11,27), as seen in other endocrine disorders with coupled bone remodeling, following treatment (37,38). The decrease in TBS following treatment in this study, despite the increase in BMD, reflects that the two measures describe different properties of bone, especially in other conditions than postmenopausal osteoporosis (4), but are in alignment with the observed high incidence and prevalence of vertebral fractures seen in acromegaly (5,31,32,33,34).…”

“…Recently, several studies have shown a marked increase in vertebral fracture prevalence and incidence for both sexes in acromegaly (5,31,32,33,34), related to the duration of disease activity and gonadal status among others. These observations underscore the complexity of a chronic and devastating disease as acromegaly, for bone as a target organ with fracture as the ultimate end point (2).…”

“…Data on BMD in acromegaly are conflicting; however, the effects of non-physiological secretion of GH and IGF-1 appear to affect the bone quality negatively (5,6). Despite normalization of bone turnover following treatment of acromegaly, the risk for vertebral fractures is still increased (5,7).…”

“…Despite normalization of bone turnover following treatment of acromegaly, the risk for vertebral fractures is still increased (5,7). One might assume that trabecular and cortical bones are differently affected by GH disorders, due to various sensitivity to the GH excess in trabecular and cortical bones.…”

“…Previous studies have revealed a differential effect of GH excess on the axial (70% trabecular bone) and appendicular skeleton (90% cortical bone) (8) and have suggested that the bone density might be inconsistent in relation to the bone area. As BMD reflects only bone quantity, and bone quality has been shown to be altered in acromegaly (9,10), the fracture risk may be underestimated by BMD (5). Biochemical markers of bone turnover can provide further reliable information on the changes in the bone remodeling, also in a high turnover state as acromegaly (11).…”