Cholecalciferol Use Is Associated With a Decreased Risk of Incident Morphometric Vertebral Fractures in Acromegaly

Abstract

Context Skeletal fragility is observed in 30% to 60% of acromegaly patients, representing an emerging complication of the disease that increases disability. Despite several studies having investigated the clinical and hormonal prognostic factors for the occurrence of vertebral fractures (VFs) in acromegaly, very few data are available on their prevention/treatment including the effect of vitamin D (VD) supplementation, which has been reported to have a fracture-protective effect in several studies in patients with osteoporosis. Objective We aimed to investigate the role of cholecalciferol (D3) supplementation in the prevention of incident VFs (i-VFs) in acromegaly. Methods A longitudinal, retrospective and multicenter study was performed on 61 acromegaly patients treated and untreated with D3 supplementation. Results Twenty-six patients were treated with D3 supplementation according to clinical guidelines. The median D3 weekly dosage was 8500 IU (interquartile range [IQR]: 3900). The median duration of D3 supplementation was 94 months (IQR: 38). At last follow-up, i-VFs were diagnosed in 14 patients (23%). I-VFs were less prevalent in patients on D3 supplementation (14.3% of cases) compared to patients not treated with D3 (85.7%; P = .02). The final level of serum V25OH-D was significantly lower in patients who developed i-VFs (28.6 ng/mL, IQR: 4.1) compared to patients who did not develop i-VFs (34.2 ng/mL, IQR: 9.6; P = .05). The logistic regression confirmed the protective role of D3 supplementation on the occurrence of i-VFs (odds ratio: 0.16; 95% CI, 0.03-0.79; P = .01). Conclusion It is likely that D3 supplementation could lead to a reduction in i-VFs in acromegaly.

Acromegaly and Bone: An Update

“…The final median 25OHD level was significantly lower in patients with incident VFs (28.6 ng/mL) than in patients without incident VFs (34.2 ng/mL). The fracture-protective effect of cholecalciferol was confirmed in logistic regression analysis (odds ratio, 0.16; 95% CI, 0.03 to 0.79) [ 26 ]. These findings suggest that at least in regions with a high prevalence of vitamin D deficiency, such as Italy [ 106 ], 25OHD should be measured in all acromegaly patients and in case of poor vitamin D status, supplementation with a standard dose of cholecalciferol should be started ( Fig.…”

“…Moreover, also very recently, in an Italian longitudinal, retrospective, and multicenter study, acromegaly patients supplemented with cholecalciferol based on general population guidelines [ 100 ] (based on clinical judgment at a median dose of 8,500 IU/week) were reported to have a lower incidence of VFs (14.3%) after a median follow-up of 94 months than untreated patients [ 26 ]. The final median 25OHD level was significantly lower in patients with incident VFs (28.6 ng/mL) than in patients without incident VFs (34.2 ng/mL).…”

“…As a matter of fact, this study was the first to show at least an association between the long-term use of standard doses [ 100 ] of a bone-active hormone such as cholecalciferol and a reduction in incident VFs, in acromegaly [ 26 ]. This is good news, since methods of preventing VFs in acromegaly—besides improving biochemical control (see below)—remain an open issue.…”

“…In fact, evidence on potential effects of bone-sparing agents in acromegaly-related osteopathy is limited (the abovementioned study on cholecalciferol was carried out in patients untreated with bone-active agents [ 26 ]) and based on retrospective observational data [ 107 ]. It was hypothesized that since the biochemical mechanism underlying the increased risk of fractures in acromegaly is suspected to be an increase in bone turnover, the use of anti-resorptive drugs could have been the most beneficial treatment [ 108 ].…”

“…Therefore, in acromegaly an increase in fracture risk, particularly at the vertebral level [ 20 ], has been progressively and consistently reported in the last 15 years [ 21 , 22 ], and this now represents one of the most relevant systemic complications of the disease [ 23 ]. In fact, since the first report of excess morphometric fractures in postmenopausal women with acromegaly [ 21 ], many subsequent papers—including several from our group [ 24 , 25 ]—have confirmed, extended, analyzed the underlying mechanism(s) and possible protective effect of treatment, making this one of the hottest topics in the area of acromegaly management [ 26 ]. Due to the current clinical impact of bone involvement in acromegaly and its increasingly wide literature coverage, it was felt necessary to critically review and update the emerging evidence on the pathophysiology, clinical history and presentation, diagnosis and treatment of acromegaly-related osteopathy through this paper.…”