Non-invasive DXA-derived bone structure assessment of acromegaly patients: a cross-sectional study

in European Journal of Endocrinology
Correspondence should be addressed to M Kužma; Email:
Restricted access


Impaired bone microarchitecture is involved in vertebral fracture (VF) development among acromegaly patients.

Aim of the study

Comparison of DXA-derived bone parameters, areal BMD (aBMD), trabecular bone score (TBS) and 3D-SHAPER parameters in acromegaly patients with healthy controls.


This cross-sectional study evaluated acromegaly patients and a control group of healthy subjects. In all subjects, a single measurement of pituitary axis hormone levels, bone turnover markers, aBMD, (total hip (TH) and lumbar spine (LS)), TBS and 3D-SHAPER of the proximal femur region was performed. All subjects underwent DXA assessment of VF using the semiquantitative approach.


One hundred six patients with acromegaly (mean age 56.6 years, BMI 30.2 kg/m2) and 104 control subjects (mean age 54.06 years, 28.4 BMI kg/m2) were included. After adjustment for weight, LS aBMD, TBS and TH trabecular volumetric BMD (vBMD) remained lower (P = 0.0048, <0.0001 and <0.0001, respectively) while cortical thickness (Cth) at TH and neck remained thicker (P = 0.006) in acromegaly patients compared with controls. The best multivariate model (model 1) discriminating patients with and without acromegaly included TBS, TH trabecular vBMD and TH Cth parameters (all P < 0.05). Twenty-two VFs (13 acromegaly subjects) were recognized. In these subjects after adjustment for age, FN aBMD, TH cortical sBMD and TH cortical vBMD remained significantly associated with the prevalent VF (OR = 2.69 (1.07–6.78), 2.84 (1.24–6.51) and 2.38 (1.11–5.10) for neck aBMD, TH cortical sBMD and TH cortical vBMD respectively)). The AUCs were similar for each parameter in this model.


Acromegaly patients, regardless of VF presence, have lower trabecular bone quantitative parameters, but those with VFs had decreased cortical density.


     European Society of Endocrinology

Related Articles

Article Information


All Time Past Year Past 30 Days
Abstract Views 621 621 117
Full Text Views 75 75 10
PDF Downloads 40 40 7



  • View in gallery

    3D SHAPER workflow. From left to right: a femur DXA acquisition, the registration process and the results (QCT-like) of the DXA-based 3D modeling process. Basically, a population-based QCT model of the proximal femur is registered onto the DXA scan of the patient. At each step of the registration process, the 2D projection of this population-based QCT model is compared with the DXA acquisition. As soon as the perfect match is obtained between projection and the DXA acquisition, the 3D patient-specific QCT-like model of the bone site is obtained. A full colour version of this figure is available at

  • View in gallery

    After adjustment for weight, (A) aBMD LS (P = 0.0048), (B) TBS (P < 0.0001) and (C) trabecular vBMD TH (P < 0.0001) remained lower in acromegaly patients compared with controls while Cth (at (D) TH and neck) remained thicker (P = 0.006). A full colour version of this figure is available at

  • View in gallery

    AUC of model 1 (TBS, TH trabecular vBMD and TH Cth) is better than those of TBS, TH trabecular vBMD and TH CTh alone.

  • View in gallery

    Differences between acromegaly subjects with vs without vertebral fracture. After adjustment for age, (A) neck aBMD, (B) TH cortical sBMD and (C) TH cortical vBMD remained significantly associated with the prevalent VF. The AUC analysis showed slight superiority of TH cortical sBMD (D). A full colour version of this figure is available at

  • View in gallery

    Average differences in both types of vBMD (trabecular and cortical) between acromegaly subjects with and without VF. Differences are shown in the mid-coronal plane. Red-yellow (respectively blue-green) colors indicate regions where vBMD is on average lower (respectively higher) for acromegaly subjects compared to controls.



MazziottiGBiagioliEMaffezzoniFSpinelloMSerraVMaroldiRFlorianiIGiustinaA. Bone turnover, bone mineral density, and fracture risk in acromegaly: a meta-analysis. Journal of Clinical Endocrinology and Metabolism 2015 100 384394. (


GiustinaAMazziottiGCanalisE. Growth hormone, insulin-like growth factors, and the skeleton. Endocrine Reviews 2008 29 535559. (


KamenickyPMazziottiGLombesMGiustinaAChansonP. Growth hormone, insulin-like growth factor-1, and the kidney: pathophysiological and clinical implications. Endocrine Reviews 2014 35 234281. (


VestergaardPMosekildeL. Fracture risk is decreased in acromegaly – a potential beneficial effect of growth hormone. Osteoporosis International 2004 15 155159. (


RiggsBLRandallRVWahnerHWJowseyJKellyPJSinghM. The nature of the metabolic bone disorder in acromegaly. Journal of Clinical Endocrinology and Metabolism 1972 34 911918. (


KayathMJVieiraJG. Osteopenia occurs in a minority of patients with acromegaly and is predominant in the spine. Osteoporosis International 1997 7 226230. (


BonadonnaSMazziottiGNuzzoMBianchiAFuscoADe MarinisLGiustinaA. Increased prevalence of radiological spinal deformities in active acromegaly: a cross-sectional study in postmenopausal women. Journal of Bone and Mineral Research 2005 20 18371844. (


MazziottiGBianchiAPorcelliTMormandoMMaffezzoniFCristianoAGiampietroADe MarinisLGiustinaA. Vertebral fractures in patients with acromegaly: a 3-year prospective study. Journal of Clinical Endocrinology and Metabolism 2013 98 34023410. (


ClaessenKMKroonHMPereiraAMAppelman-DijkstraNMVerstegenMJKloppenburgMHamdyNABiermaszNR. Progression of vertebral fractures despite long-term biochemical control of acromegaly: a prospective follow-up study. Journal of Clinical Endocrinology and Metabolism 2013 98 48084815. (


MelmedSCasanuevaFFKlibanskiABronsteinMDChansonPLambertsSWStrasburgerCJWassJAGiustinaA. A consensus on the diagnosis and treatment of acromegaly complications. Pituitary 2013 16 294302. (


UelandTBollerslevJGodangKMullerFFrolandSSAukrustP. Increased serum osteoprotegerin in disorders characterized by persistent immune activation or glucocorticoid excess – possible role in bone homeostasis. European Journal of Endocrinology 2001 145 685690. (


StepanJMarekJHavranekTDolezalVPacovskyV. Bone isoenzyme of serum alkaline phosphatase in acromegaly. Clinica Chimica Acta 1979 93 355363. (


ScillitaniAChiodiniICarnevaleVGiannatempoGMFruscianteVVillellaMPileriMGuglielmiGDi GiorgioAModoniS et al. Skeletal involvement in female acromegalic subjects: the effects of growth hormone excess in amenorrheal and menstruating patients. Journal of Bone and Mineral Research 1997 12 17291736. (


DiamondTNeryLPosenS. Spinal and peripheral bone mineral densities in acromegaly: the effects of excess growth hormone and hypogonadism. Annals of Internal Medicine 1989 111 567573. (


Dalle CarbonareLMichelettiVCosaroEValentiMTMottesMFranciaGDaviMV. Bone histomorphometry in acromegaly patients with fragility vertebral fractures. Pituitary 2018 21 5664. (


MaffezzoniFMaddaloMFraraSMezzoneMZorzaIBaruffaldiFDogliettoFMazziottiGMaroldiRGiustinaA. High-resolution-cone beam tomography analysis of bone microarchitecture in patients with acromegaly and radiological vertebral fractures. Endocrine 2016 54 532542. (


MadeiraMNetoLVde Paula Paranhos NetoFBarbosa LimaICCarvalho de MendoncaLMGadelhaMRFleiuss de FariasML. Acromegaly has a negative influence on trabecular bone, but not on cortical bone, as assessed by high-resolution peripheral quantitative computed tomography. Journal of Clinical Endocrinology and Metabolism 2013 98 17341741. (


MalgoFHamdyNATPapapoulosSEAppelman-DijkstraNM. Bone material strength index as measured by impact microindentation is low in patients with fractures irrespective of fracture site. Osteoporosis International 2017 28 24332437. (


GodangKOlarescuNCBollerslevJHeckA. Treatment of acromegaly increases BMD but reduces trabecular bone score: a longitudinal study. European Journal of Endocrinology 2016 175 155164. (


HongARKimJHKimSWKimSYShinCS. Trabecular bone score as a skeletal fragility index in acromegaly patients. Osteoporosis International 2016 27 11231129. (


HumbertLMartelliYFonollaRSteghoferMDi GregorioSMaloufJRomeraJBarqueroLM. 3D-DXA: assessing the femoral shape, the trabecular macrostructure and the cortex in 3D from DXA images. IEEE Transactions on Medical Imaging 2017 36 2739. (


FreitasLAmorimTHumbertLFonollaRFlourisADMetsiosGSJamurtasAZKoutedakisY. Cortical and trabecular bone analysis of professional dancers using 3D-DXA: a case-control study. Journal of Sports Sciences 2018 Epub. (


GifreLHumbertLMuxiADel RioLVidalJPortellEMonegalAGuanabensNPerisP. Analysis of the evolution of cortical and trabecular bone compartments in the proximal femur after spinal cord injury by 3D-DXA. Osteoporosis International 2018 29 201209. (


HumbertLHazrati MarangalouJDel Rio BarqueroLMvan LentheGHvan RietbergenB. Technical note: cortical thickness and density estimation from clinical CT using a prior thickness-density relationship. Medical Physics 2016 43 1945. (


KatznelsonLLawsERJr.MelmedSMolitchMEMuradMHUtzAWassJA & Endocrine Society. Acromegaly: an Endocrine Society Clinical Practice Guideline. Journal of Clinical Endocrinology and Metabolism 2014 99 39333951. (


ChamberlainJJRhinehartASShaeferCFJrNeumanA. Diagnosis and management of diabetes: synopsis of the 2016 American Diabetes Association standards of medical care in diabetes. Annals of Internal Medicine 2016 164 542552. (


TreeceGMGeeAH. Independent measurement of femoral cortical thickness and cortical bone density using clinical CT. Medical Image Analysis 2015 20 249264. (


PooleKETreeceGMGeeAHBrownJPMcClungMRWangALibanatiC. Denosumab rapidly increases cortical bone in key locations of the femur: a 3D bone mapping study in women with osteoporosis. Journal of Bone and Mineral Research 2015 30 4654. (


NicksKMAminSMeltonLJ3rdAtkinsonEJMcCreadyLKRiggsBLEngelkeKKhoslaS. Three-dimensional structural analysis of the proximal femur in an age-stratified sample of women. Bone 2013 55 179188. (


GenantHKJergasMPalermoLNevittMValentinRSBlackDCummingsSR. Comparison of semiquantitative visual and quantitative morphometric assessment of prevalent and incident vertebral fractures in osteoporosis the Study of Osteoporotic Fractures Research Group. Journal of Bone and Mineral Research 1996 11 984996. (


ReaJALiJBlakeGMSteigerPGenantHKFogelmanI. Visual assessment of vertebral deformity by X-ray absorptiometry: a highly predictive method to exclude vertebral deformity. Osteoporosis International 2000 11 660668. (


Hoyer-KuhnHKnoopKSemlerOKuhrKHellmichMSchoenauEKoerberF. Comparison of DXA scans and conventional X-rays for spine morphometry and bone age determination in children. Journal of Clinical Densitometry 2016 19 208215. (


Google Scholar