Loss of bone mass in patients with Klinefelter's syndrome despite sufficient testosterone replacement

Wong, F. H. W.; Pun, Kong-Pang; Wang, C.

doi:10.1007/bf01623169

Cited by 74 publications

(33 citation statements)

References 18 publications

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“…In both situations, although testosterone was synthesised and the androgen receptor (AR) unaffected, there was abnormal skeletal development and marked osteopenia. Furthermore, although there are reports that testosterone treatment improved bone mineral density in hypogonadal men (Behre et al 1997), osteoporotic patients with Klinefelter's disease did not respond to this treatment (Wong et al 1993), nor was it effective in treating males with aromatase deficiency (Carani et al 1997). They, however, responded to oestrogen.…”

Section: Importance Of Oestrogens For Maintaining Bone In Men and Womenmentioning

confidence: 99%

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

Byers¹,

Hoyland²,

Braidman³

2001

Journal of Endocrinology

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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...

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Section: Importance Of Oestrogens For Maintaining Bone In Men and Womenmentioning

confidence: 99%

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

Byers¹,

Hoyland²,

Braidman³

2001

Journal of Endocrinology

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“…Our results on the age dependency of the efficacy of androgen substitution on BMD underline the necessity to commence androgen substitution in hypogonadism as early as possible, albeit in adolescence achieving an appropriate final height must be kept in mind. Nevertheless, the results of our study indicate that delayed onset of substitution might not be able to normalize BMD any more, even when androgens are given over extended periods of time [8, 23, 24]. …”

Section: Discussionmentioning

confidence: 88%

“…Despite the widespread assumption that testosterone substitution increases the bone mineral density (BMD) in male hypogonadism, evidence is based on very small patient numbers [5, 6, 7], not unanimously [8], and a recent review concluded that an anabolic effect on bone is not obvious from the available data [9]. Furthermore, so far no study exists investigating the effects of different modes of androgen substitution on the BMD.…”

Section: Introductionmentioning

confidence: 99%

Osteoporosis in Male Hypogonadism: Responses to Androgen Substitution Differ among Men with Primary and Secondary Hypogonadism

Schubert

Bullmann²,

Minnemann³

et al. 2003

Horm Res Paediatr

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Background: No randomized study exists comparing the effects of different modes of androgen substitution on bone mineral density (BMD). Methods: We performed a prospective, randomized, trial assigning 53 hypogonadal men to the following treatment groups: mesterolone 100 mg p.o. daily, testosterone undecanoate 160 mg p.o. daily, testosterone enanthate 250 mg i.m. every 21 days, or a single subcutaneous implantation of 1,200 mg crystalline testosterone. The BMD was determined by peripheral quantitative computed tomography. Results: At baseline, men with secondary hypogonadism (n = 33) had a lower BMD (–1.52 ± 0.23 SDS; Z-scores) than men with primary hypogonadism (n = 20, –0.87 ± 0.23 SDS, p < 0.01). In men with primary hypogonadism, the BMD increased dose dependently (crystalline testosterone +7.0 ± 1.3%, testosterone enanthate +4.8 ± 0.2%, testosterone undecanoate +3.4 ± 2.5%, mesterolone +0.8 ± 1.6%) after 6 months of therapy. Only secondary hypogonadal men treated with testosterone enanthate experienced an increase of the BMD. Conclusions: In primary hypogonadal men the BMD responds dose dependently to testosterone substitution, whereas in secondary hypogonadism only testosterone enanthate treatment significantly increased the BMD.

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“…These considerations suggest that suboptimal testosterone replacement dosage may be an overlooked determinant of previously reported inadequate bone density response to testosterone rather than unexplained independent bone effects of the underlying disorders causing hypogonadism (14,46). Recognizing the importance of sustaining adequate testosterone treatment over prolonged periods may also lead to reconsideration of claims that bone deficits occurring in adolescence (prior to acquisition of peak bone mass (47)) may not be correctable in the light of more effective treatment.…”

Section: Discussionmentioning

confidence: 99%

Adequacy of androgen replacement influences bone density response to testosterone in androgen-deficient men

Aminorroaya

Kelleher²,

Conway³

et al. 2005

eur j endocrinol

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Objective: Androgen deficiency (AD) leads to bone loss and contributes to osteoporotic fractures in men. Although low bone mineral density (BMD) in AD men is improved by testosterone replacement, the responses vary between individuals but the determinants of this variability are not well defined. Design and methods: Retrospective review of dual energy X-ray absorptiometry (DEXA) of the lumbar spine and proximal femur in men with established AD requiring regular androgen replacement therapy (ART). After a DEXA scan all men were treated with testosterone implants (800 mg, , 6 month intervals). Patients were classified as having a congenital, childhood, or post-pubertal onset, as well as according to the adequacy of treatment prior to their first DEXA scan as untreated, partially treated or well treated. Results: Men with AD requiring regular ART (n ¼ 169, aged 46.3^1.1 years, range 22 -84 years) underwent a DEXA scan prior to being treated with testosterone implants (800 mg, ,6 month intervals). In cross-sectional analysis at the time of the first DEXA scan untreated men (n ¼ 24) had significantly reduced age-adjusted BMD at all four sites (L1 -L4, femoral neck, Ward's triangle and trochanter). Well-treated men (n ¼ 77) had significantly better age-adjusted BMD at all four sites compared with those who were partially treated (n ¼ 66) or untreated (n ¼ 24) with their ageadjusted BMD being normalized. In a longitudinal assessment of men (n ¼ 60) who had two or more serial DEXA scans, at the second DEXA scan after a median of 3 years, men who were previously partially treated (n ¼ 19) or untreated (n ¼ 11) had proportionately greater improvements in BMD, significantly for Ward's triangle (P ¼ 0.025) and the trochanter (P ¼ 0.044) compared with men (n ¼ 30) previously well treated. Conclusions: The present study demonstrates a positive relationship between adequacy of testosterone replacement and BMD in men with overt organic AD. Additionally, the BMD of well-treated AD men approximates that of age-matched non-AD controls. The greatest BMD gains are made by those who have been either untreated or partially treated, and optimal treatment over time (median 3 years) normalizes BMD to the level expected for healthy men of the same age.European Journal of Endocrinology 152 881-886

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Loss of bone mass in patients with Klinefelter's syndrome despite sufficient testosterone replacement

Cited by 74 publications

References 18 publications

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

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

Osteoporosis in Male Hypogonadism: Responses to Androgen Substitution Differ among Men with Primary and Secondary Hypogonadism

Adequacy of androgen replacement influences bone density response to testosterone in androgen-deficient men

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