Bone mineral density in acromegaly: the effect of gender, disease activity and gonadal status

Scillitani, Alfredo; Battista, Claudia; Chiodini, Iacopo; Carnevale, Vincenzo; Fusilli, Saverio; Ciccarelli, Enrica; Terzolo, Massimo; Oppizzi, G.; Arosio, Maura; Gasperi, Maurizio; Arnaldi, Giorgio; Colao, Annamaria; Baldelli, Roberto; Ghiggi, Maria Rosaria; Gaia, Daniela; Somma, Carolina Di; Trischitta, Vincenzo; Liuzzi, Antonio

doi:10.1046/j.1365-2265.2003.01777.x

Cited by 60 publications

(48 citation statements)

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“…However, a recent study demonstrated a high prevalence of vertebral fractures in postmenopausal women with acromegaly in relation to disease activity (21). Thus, gonadal status has been proposed to be an important determinant of excess GH (7,13,15,17), and it is possible that trabecular bone, with its more intimate contact with the circulation, is influenced by sex steroids to a greater extent.…”

Section: Introductionmentioning

confidence: 99%

“…In fact, acromegaly was traditionally associated with osteoporosis (12)(13)(14). Later studies have revealed a differential effect of GH excess on the axial (70% trabecular bone) and appendicular skeleton (90% cortical bone) with unchanged or reduced vertebral bone density and increased forearm bone density (1,3,(13)(14)(15)(16)(17), while some studies show no differences in acromegalic patients compared with normal controls (4,18,19). However, measurement of bone mineral density (BMD) in the axial skeleton, as an indicator of trabecular bone mass, may be overestimated in endocrine disorders affecting bone size and the distribution between trabecular and cortical envelopes.…”

Section: Introductionmentioning

confidence: 99%

“…Details on gonadal status in patients and controls are given in Table 1. The duration of acromegaly (nZ55) was estimated to be (mean and range) 8 years (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). The study was approved by the local ethical committee and conducted according to the Declaration of Helsinki II.…”

Section: Subjectsmentioning

confidence: 99%

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Serum GH and IGF-I are significant determinants of bone turnover but not bone mineral density in active acromegaly: a prospective study of more than 70 consecutive patients

Ueland

Fougner

Godang³

et al. 2006

eur j endocrinol

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Objective: Acromegaly is characterized by a persistent hypersecretion of GH and provides information on long-term effects of GH on bone metabolism. The aim of this study was to examine the effect of gonadal status and disease activity on bone metabolism in active acromegaly. Methods: Seventy-three consecutive patients with active acromegaly: 40 women and 33 men (50G13 (meanGS.D.) and 49G10 years respectively) were evaluated and compared with age-, sex-, and body mass index (BMI)-matched controls by X-ray absorptiometry and biochemical analysis (markers of disease activity and bone turnover). Results: We found that bone turnover, as evaluated by biochemical bone markers, is coupled and markedly increased in relation to disease activity in active acromegaly. Acromegalic women, but not men, were characterized by an increased bone area and slightly decreased bone mineral content resulting in significantly decreased bone mineral density (BMD) in the ultradistal radius, proximal radius, and total body. No differences in bone turnover or BMD were found between eu-and hypogonadal subjects. Multivariate analysis identified age, BMI, and gender as independent predictors of total BMD in acromegaly. Conclusion: Our study demonstrates a decreased total body BMD in women, not men, with active acromegaly, regardless of gonadal status or disease activity. Bone turnover is markedly increased in relation to disease activity, possibly counteracting the anabolic effects of excess GH/IGF-I in these subjects. We suggest more focus on biomechanical analyses when investigating endocrine disorders affecting bone size and distribution between compartments.European Journal of Endocrinology 155 709-715

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Serum GH and IGF-I are significant determinants of bone turnover but not bone mineral density in active acromegaly: a prospective study of more than 70 consecutive patients

Ueland

Fougner

Godang³

et al. 2006

eur j endocrinol

View full text Add to dashboard Cite

show abstract

“…In active acromegaly, high circulating concentrations of GH and IGF1 are associated with increased cortical BMD (6)(7)(8)(9)(10). The reported effects of GH/IGF1 excess on trabecular BMD are more variable, with studies reporting either increased or decreased BMD at trabecular sites possibly due to the variable presence of hypogonadism (1,(3)(4)(5)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

“…It has also been suggested that the anabolic effects of GH on bone mineral density (BMD) may be sustained after cure of acromegaly (1)(2)(3)(4)(5), but duration of follow-up was relatively short in the majority of studies. The effects of GH excess on BMD appear to be less consistent.…”

Section: Introductionmentioning

confidence: 99%

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

Wassenaar

Biermasz

Hamdy

et al. 2011

European Journal of Endocrinology

134

100

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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.

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Growth hormone mediates pubertal skeletal development independent of hepatic IGF-1 production

Courtland

Sun

Beth-On

et al. 2010

Journal of Bone and Mineral Research

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Deficiencies in either growth hormone (GH) or insulin-like growth factor 1 (IGF-1) are associated with reductions in bone size during growth in humans and animal models. Liver-specific IGF-1-deficient (LID) mice, which have 75% reductions in serum IGF-1, were created previously to separate the effects of endocrine (serum) IGF-1 from autocrine/paracrine IGF-1. However, LID mice also have two- to threefold increases in GH, and this may contribute to the observed pubertal skeletal phenotype. To clarify the role of GH in skeletal development under conditions of significantly reduced serum IGF-1 levels (but normal tissue IGF-1 levels), we studied the skeletal response of male LID and control mice to GH inhibition by pegvisomant from 4 to 8 weeks of age. Treatment of LID mice with pegvisomant resulted in significant reductions in body weight, femur length (Le), and femur total area (Tt.Ar), as well as further reductions in serum IGF-1 levels by 8 weeks of age, compared with the mean values of vehicle-treated LID mice. Reductions in both Tt.Ar and Le were proportional after treatment with pegvisomant. On the other hand, the relative amount of cortical tissue formed (RCA) in LID mice treated with pegvisomant was significantly less than that in both vehicle-treated LID and control mice, indicating that antagonizing GH action, either directly (through GH receptor signaling inhibition) or indirectly (through further reductions in serum/tissue IGF-1 levels), results in disproportionate reductions in the amount of cortical bone formed. This resulted in bones with significantly reduced mechanical properties (femoral whole-bone stiffness and work to failure were markedly decreased), suggesting that compensatory increases of GH in states of IGF-1 deficiency (LID mice) act to protect against a severe inhibition of bone modeling during growth, which otherwise would result in bones that are too weak for normal and/or extreme loading conditions. © 2011 American Society for Bone and Mineral Research.

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Bone mineral density in acromegaly: the effect of gender, disease activity and gonadal status

Abstract: The anabolic effect of GH excess on bone in acromegalic patients is: (i) gender-independent; (ii) evident at the spine only in eugonadal regardless of disease activity; (iii) evident at femoral neck only in the presence of active disease regardless of gonadal status.

Cited by 60 publications

References 17 publications

Serum GH and IGF-I are significant determinants of bone turnover but not bone mineral density in active acromegaly: a prospective study of more than 70 consecutive patients

Serum GH and IGF-I are significant determinants of bone turnover but not bone mineral density in active acromegaly: a prospective study of more than 70 consecutive patients

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

Growth hormone mediates pubertal skeletal development independent of hepatic IGF-1 production

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