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Bone health in ageing men

Abstract

Osteoporosis does not only affect postmenopausal women, but also ageing men. The burden of disease is projected to increase with higher life expectancy both in females and males. Importantly, osteoporotic men remain more often undiagnosed and untreated compared to women. Sex steroid deficiency is associated with bone loss and increased fracture risk, and circulating sex steroid levels have been shown to be associated both with bone mineral density and fracture risk in elderly men. However, in contrast to postmenopausal osteoporosis, the contribution of relatively small decrease of circulating sex steroid concentrations in the ageing male to the development of osteoporosis and related fractures, is probably only minor. In this review we provide several clinical and preclinical arguments in favor of a ‘bone threshold’ for occurrence of hypogonadal osteoporosis, corresponding to a grade of sex steroid deficiency that in general will not occur in many elderly men. Testosterone replacement therapy has been shown to increase bone mineral density in men, however data in osteoporotic ageing males are scarce, and evidence on fracture risk reduction is lacking. We conclude that testosterone replacement therapy should not be used as a sole bone-specific treatment in osteoporotic elderly men.

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Data Availability

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Code Availability

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Abbreviations

25(OH)D:

25-hydroxyvitaminD

aBMD:

areal bone mineral density

ADT:

androgen deprivation therapy

AR:

androgen receptor

BioE2:

bioavailable estradiol

BioT:

bioavailable testosterone

BMD:

bone mineral density

BMI:

body mass index

BTM:

bone turnover marker

DHT:

dihydrotestosterone

DXA:

dual X-ray absorptiometry

E1:

estrone

E2:

estradiol

EMAS:

European male ageing study

ERɑ:

estrogen receptor alpha

FN:

femoral neck

FRAX:

Fracture Risk Assessment Tool

IA:

immunoassay

LOH:

late onset hypogonadism

LS:

lumbar spine

MOF:

major osteoporotic fracture

MrOS:

osteoporotic fractures in men study

MS:

mass spectrometry

PBM:

peak bone mass

pQCT:

peripheral quantitative computed tomography

QCT:

quantitative computed tomography

RCT:

randomized controlled trial

SARM:

selective androgen receptor modulator

SD:

standard deviation

SERM:

selective estrogen receptor modulator

SHBG:

sex hormone binding globulin

SNP:

single nucleotide polymorphism

T:

testosterone

TBS:

trabecular bone score

TH:

total hip

TRT:

testosterone replacement therapy

vBMD:

volumetric bone mineral density

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Funding

KD receives a PhD fellowship Fundamental Research from Flanders Research Foundation (FWO 1196522N). This work was funded by FWO research grant (G099518N) and by KU Leuven grant (C14/19/100).

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DV conceived the idea for the manuscript. KD and DV performed literature search. KD wrote the first draft with assistance of DV. All authors reviewed and edited the manuscript before submission.

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Correspondence to Dirk Vanderschueren.

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David, K., Narinx, N., Antonio, L. et al. Bone health in ageing men. Rev Endocr Metab Disord (2022). https://doi.org/10.1007/s11154-022-09738-5

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Keywords

  • Male osteoporosis
  • Ageing
  • Bone health
  • Sex steroids
  • Testosterone replacement therapy