Long-Term Bone Loss in Men: Effects of Genetic and Environmental Factors

Slemenda, Charles W.; Christian, Joe C.; Reed, Terry; Reister, Teresa K.; Williams, Christopher J.; Johnston, C. Conrad

doi:10.7326/0003-4819-117-4-286

Cited by 200 publications

(98 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…All of the previous studies evaluating heritability of bone mass or longitudinal bone loss have considered age as a simple covariate in their models. (3)(4)(5)(6)(7)(8)(9)(10)12,(19)(20)(21)(22)(23) The results of our study also show that age can be treated as a simple covariate for cross-sectional BMD measures because heritability estimates change little across a 40-year age span (all of them are generally between 70% and 90%). However, the age effect has to be considered for the longitudinal changes, as the model fits change completely with advanced aging.…”

Section: Discussionmentioning

confidence: 56%

“…(3)(4)(5) However, it is difficult to interpret the genetic effects on bone loss from these studies because these cross-sectional studies more reflect variations in peak bone mass rather than bone loss. Previous longitudinal studies were underpowered due to small sample size (6)(7)(8) or young age range of participants. (9) A study in peri-and postmenopausal women followed for 1 to 10 years showed a significant heritability for BMD changes in lumbar spine and forearm but not in the hip area.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of age on genetic influence on bone loss over 17 years in women: The Healthy Ageing Twin Study (HATS)

Moayyeri

Hammond

Hart

et al. 2012

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

The rate of bone loss varies across the aging period via multiple complex mechanisms. Therefore, the role of genetic factors on bone loss may also change similarly. In this study, we investigated the effect of age on the genetic component of bone loss in a large twin-based longitudinal study. During 17 years of follow-up in TwinsUK and Healthy Ageing Twin Study (HATS), 15,491 hip and lumbar spine dualenergy X-ray absorptiometry (DXA) scans were performed in 7056 twins. Out of these subjects, 2716 female twins aged >35 years with at least two scans separated for >4 years (mean follow-up 9.7 years) were included in this analysis. We used a mixed-effects randomcoefficients regression model to predict hip and spine bone mineral density (BMD) values for exact ages of 40, 45, 50, 55, 60, 65, 70, 75, and 80 years, with adjustment for baseline age, weight, height, and duration of hormone replacement therapy. We then estimated heritability of the changes in BMD measures between these age ranges. Heritability estimates for cross-sectional hip and spine BMD were high (ranging between 69% and 88%) at different ages. Heritability of change of BMD was lower and more variable, generally ranging from 0% to 40% for hip and 0% to 70% for spine; between age 40 and 45 years genetic factors explained 39.9% (95% confidence interval [CI], 25%-53%) of variance of BMD loss for total hip, 46.4% (95% CI, 32%-58%) for femoral neck, and 69.5% (95% CI, 59%-77%) for lumbar spine. These estimates decreased with increasing age, and there appeared to be no heritability of BMD changes after the age of 65 years. There was some evidence at the spine for shared genetic effects between cross-sectional and longitudinal BMD. Whereas genetic factors appear to have an important role in bone loss in early postmenopausal women, nongenetic mechanisms become more important determinants of bone loss with advanced age. ß

show abstract

Section: Discussionmentioning

confidence: 56%

Section: Introductionmentioning

confidence: 99%

Effects of age on genetic influence on bone loss over 17 years in women: The Healthy Ageing Twin Study (HATS)

Moayyeri

Hammond

Hart

et al. 2012

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

show abstract

“…This has been studied extensively in this context, but mostly in women. Of the few studies with men, investigations of elderly male twins demonstrated that environmental and lifestyle factors were more important than inheritance in determining bone loss (Christian et al 1989, Slemenda et al 1992. Even in elderly women it has been suggested that the contribution of genetic factors to bone turnover and bone loss is likely to be small (Garnero et al 1996).…”

Section: Peak Bone Mass As a Determinant Of Osteoporosismentioning

confidence: 99%

Osteoporosis in men: a cellular endocrine perspective of an increasingly common clinical problem

Byers¹,

Hoyland²,

Braidman³

2001

Journal of Endocrinology

View full text Add to dashboard Cite

Although it has been accepted that osteoporosis is common in women, only recently have we become aware that it is also widespread in men; one in twelve men in the UK have osteoporosis. In many cases, there are recognisable causes for their osteoporosis, but a significant proportion (approximately one third) of these men have idiopathic disease. A major problem is that these cases are difficult to treat. An important therapeutic strategy would be to identify men at risk from osteoporosis sufficiently early, so that they can begin preventative measures. Moreover, development of novel means of treating these men would be an important clinical advance. With the emphasis on osteoporosis in women, however, the cellular and molecular basis for male idiopathic osteoporosis (MIO) is still poorly understood. Nevertheless, there are some aspects of skeletal regulation which may be specific for men and which could form the basis for addressing these problems. Thus, the importance of oestrogen in maintaining the adult skeleton in men as well as women implies that bone cells in men can respond to low levels of the hormone. Both oestrogen receptor (ER) and are expressed in bone in vivo, which may be important for oestrogen action on bone in men. Furthermore, in osteoporosis generally, there is increasing evidence for defective osteoblast differentiation such that there is a surfeit of adipocytes over osteoblasts. A low peak bone mass is a powerful risk factor for osteoporosis in later life; bone formation and, by implication, osteoblast differentiation, is key to the mechanism by which it is accrued. GH and IGFs are important for regulating osteoblast differentiation. Evidence now suggests that they are associated with bone mineral density, particularly in men. The genes for ERs, GH and IGF-I might be useful candidates with which we can begin to detect men at risk from osteoporosis. Furthermore, the mechanisms by which oestrogen, GH and IGF-I regulate the male skeleton could provide the basis for developing novel means of treating MIO. Journal of Endocrinology (2001) 168, 353-362 Features of male osteoporosisOsteoporosis affects approximately one third of women in the United Kingdom, and this has overshadowed the disease in men. It is now recognised that one in twelve men in Western countries have osteoporosis; 30% of all hip fractures are in men (Eastell et al. 1998) and it accounts for at least one quarter of the total £1 billion burden of osteoporosis on the National Health Service in the United Kingdom. Moreover, recent observations of Ismail et al. (2000) indicate that the effects of the disease in men are at least as severe as in women. There are well-recognised risk factors for men; for example, treatment with antiinflammatory steroids, tobacco and alcohol consumption, and hypogonadism. At least a third of men with osteoporosis, however, have idiopathic disease. Why certain men have male idiopathic osteoporosis (MIO) and whether suitable treatment can be developed for them are major questions. Due to the emph...

show abstract

“…Most animal models have used females and osteoporosis in the male has been largely ignored despite the fact that it is a growing problem in older men (Slemenda et al, 1992) and men with delayed puberty (Finkelstein et al, 1992). Future studies using male animals would be of interest but the practicality and availability of male sheep (rams) might be a limiting factor for this model to study the different aspects of osteoporosis in men.…”

Section: Sheepmentioning

confidence: 99%

Animal models of osteoporosis - necessity and limitations

2001

eCM

233

View full text Add to dashboard Cite

There is a great need to further characterise the available animal models for postmenopausal osteoporosis, for the understanding of the pathogenesis of the disease, investigation of new therapies (e.g. selective estrogen receptor modulators (SERMs)) and evaluation of prosthetic devices in osteoporotic bone. Animal models that have been used in the past include non-human primates, dogs, cats, rodents, rabbits, guinea pigs and minipigs, all of which have advantages and disadvantages. Sheep are a promising model for various reasons: they are docile, easy to handle and house, relatively inexpensive, available in large numbers, spontaneously ovulate, and the sheep's bones are large enough to evaluate orthopaedic implants. Most animal models have used females and osteoporosis in the male has been largely ignored. Recently, interest in development of appropriate prosthetic devices which would stimulate osseointegration into osteoporotic, appendicular, axial and mandibular bone has intensified. Augmentation of osteopenic lumbar vertebrae with bioactive ceramics (vertebroplasty) is another area that will require testing in the appropriate animal model. Using experimental animal models for the study of these different facets of osteoporosis minimizes some of the difficulties associated with studying the disease in humans, namely time and behavioral variability among test subjects. New experimental drug therapies and orthopaedic implants can potentially be tested on large numbers of animals subjected to a level of experimental control impossible in human clinical research.

show abstract

Long-Term Bone Loss in Men: Effects of Genetic and Environmental Factors

Abstract: Bone loss in men during mid-life is determined, at least in part, by environmental factors, including smoking, alcohol intake, and, possibly, physical activity. Rates of bone loss were similar within twin pairs, apparently because of a shared environment.

Cited by 200 publications

References 26 publications

Effects of age on genetic influence on bone loss over 17 years in women: The Healthy Ageing Twin Study (HATS)

Effects of age on genetic influence on bone loss over 17 years in women: The Healthy Ageing Twin Study (HATS)

Osteoporosis in men: a cellular endocrine perspective of an increasingly common clinical problem

Animal models of osteoporosis - necessity and limitations

Contact Info

Product

Resources

About