Does Hypogonadism Contribute to the Occurrence of a Minimal Trauma Hip Fracture in Elderly Men?

Stanley, Holly L.; Schmitt, Brian P.; Poses, Roy M.; Deiss, William P.

doi:10.1111/j.1532-5415.1991.tb02698.x

Cited by 242 publications

(90 citation statements)

References 40 publications

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“…Indeed, older men with hypogonadism have been shown to be at increased risk of hip fracture. 15 This increased risk of fracture is likely due to a combination of decreased muscle mass, decreased strength, and osteoporosis from decreased serum T. T therapy in this population might improve recovery by improving muscle mass and strength and preventing prolonged bed-ridden status.…”

Section: Discussionmentioning

confidence: 99%

Preoperative Supraphysiological Testosterone in Older Men Undergoing Knee Replacement Surgery

Amory¹,

Chansky

et al. 2002

J American Geriatrics Society

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OBJECTIVES:Older patients undergoing knee replacement surgery can recover more slowly than younger patients and require extended rehabilitation. Because administration of supraphysiological testosterone (T) dramatically increases strength, we hypothesized that preoperative T therapy would improve functional recovery and reduce hospital stay in older men undergoing knee replacement surgery. DESIGN: Double-blinded, placebo-controlled pilot trial. SETTING: A Veterans Affairs orthopedics clinic and inpatient postoperative unit. PARTICIPANTS: Twenty-five men, mean age 70, undergoing elective knee replacement. INTERVENTION: Preoperative, supraphysiological T administration (600 mg T enanthate intramuscularly weekly for 4 weeks) or sesame oil placebo. MEASUREMENTS: Length of hospital stay and functional ability by Functional Independence Measure (FIM) score. RESULTS: Mean length of hospital stay Ϯ standard deviation was nonsignificantly reduced in the T group (5.9 Ϯ 2.4 days vs 6.8 Ϯ 2.5 days; P ϭ .15). At postoperative Day 3, there was a significant improvement in ability to stand (mean FIM score 5.2 Ϯ 1.0 vs 4.0 Ϯ 1.1; P ϭ .04) and trends towards improvements in walking and stair climbing in the T group. There were no complications attributable to T therapy. CONCLUSIONS: In older men undergoing knee replacement surgery, preoperative supraphysiological T administration may confer some clinical benefit. Future studies using longer courses of preoperative T administration in larger numbers of older men undergoing knee replacement surgery are warranted. J Am Geriatr Soc 50:1698-1701, 2002. Key words: arthritis; arthroplasty; FIM; rehabilitation K nee replacement surgery is associated with beneficial outcomes in appropriately selected patients. More than 100,000 knee replacements are performed yearly in the United States, 1 and 90% of these patients are aged 55 and older. 2,3 Older patients have slower recovery of ambulatory function and strength in knee extensors than younger patients 4,5 and are more likely to require prolonged hospitalization or inpatient rehabilitation postoperatively. 4 Levels of testosterone (T) fall as men age, 6 and supplementation with T can improve strength in older hypogonadal men. 7 Recently, T was shown to improve rehabilitation outcomes in older men with low-normal serum T levels during an 8-week inpatient rehabilitation stay. 8 Muscle strength and protein synthesis occur shortly after administration of exogenous T, 9 and relatively low dosages of T result in improved strength after 1 month in older men. 10 In young men, supraphysiological dosing of T enanthate results in dramatic exercise-independent increases in strength, muscle size and fat-free body mass without adverse affects on lipids, prostate-specific antigen (PSA), mood or behavior. 11,12 Because strength plays such a pivotal role in recovery from a joint replacement operation, we hypothesized that short-term supraphysiological T therapy might improve postoperative outcomes in older men undergoing knee replacement surgery. Therefor...

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Section: Discussionmentioning

confidence: 99%

Preoperative Supraphysiological Testosterone in Older Men Undergoing Knee Replacement Surgery

Amory¹,

Chansky

et al. 2002

J American Geriatrics Society

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“…Similarly, castration in men causes increased bone resorption and bone loss (11,12). In addition, low levels of testosterone correlate with decreased bone mineral density and increased risk of fracture in elderly men (13)(14)(15). As in humans, orchidectomy in the rat causes bone loss that is characterized by increased endosteal bone resorption, as well as loss of trabecular bone and increased osteoclast numbers.…”

Section: Introductionmentioning

confidence: 99%

Regulation of interleukin-6, osteoclastogenesis, and bone mass by androgens. The role of the androgen receptor.

Bellido¹,

Jilka²,

Boyce³

et al. 1995

J. Clin. Invest.

409

218

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Interleukin-6 is an essential mediator of the bone loss caused by loss of estrogens. Because loss of androgens also causes bone loss, we have examined whether the IL-6 gene is regulated by androgens, and whether IL-6 plays a role in the bone loss caused by androgen deficiency. Both testosterone and dihydrotestosterone inhibited IL-6 production by murine bone marrow-derived stromal cells. In addition, testosterone, dihydrotestosterone, and adrenal androgens inhibited the expression of a chloramphenicol acetyl transferase reporter plasmid driven by the human IL-6 promoter in HeLa cells cotransfected with an androgen receptor expression plasmid; however, these steroids were ineffective when the cells were cotransfected with an estrogen receptor expression plasmid. In accordance with the in vitro findings, orchidectomy in mice caused an increase in the replication of osteoclast progenitors in the bone marrow which could be prevented by androgen replacement or administration of an IL-6 neutralizing antibody. Moreover, bone histomorphometric analysis of trabecular bone revealed that, in contrast to IL-6 sufficient mice which exhibited increased osteoclast numbers and bone loss following orchidectomy, IL-6 deficient mice (generated by targeted gene disruption) did not. This evidence demonstrates that male sex steroids, acting through the androgen-specific receptor, inhibit the expression of the IL-6 gene; and that IL-6 mediates the upregulation of osteoclastogenesis and therefore the bone loss caused by androgen deficiency, as it does in estrogen deficiency. (J.

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“…Biochemical evidence of hypogonadism is found in about 20% of men with vertebral fractures [2] and up to 50% of men with hip fractures [3,4], often without other clinical features of gonadal failure. In cell culture studies using human osteoblastlike cells from both men and women [5][6][7], specific androgen receptors can be identified by nuclear and cytosolic binding assays (Table 1).…”

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confidence: 99%

Sex Hormones and Osteoporosis in Men

et al. 1998

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Osteoporosis in men is a common disorder, the incidence of which is increasing. Bone is lost with advancing age in men as well as in women, leading to an increased risk of fracture after minimal trauma. Recent epidemiological data from North America suggests a lifetime risk of fracture of the hip, spine, or forearm of 13.1% in white men aged 50 [1]. Despite the considerable public health burden attributable to these fractures, our understanding of their pathogenesis is incomplete and there is no established treatment for osteoporosis in men.Androgen deficiency is thought to play an important role in many cases of male osteoporosis. Biochemical evidence of hypogonadism is found in about 20% of men with vertebral fractures [2] and up to 50% of men with hip fractures [3,4], often without other clinical features of gonadal failure. In cell culture studies using human osteoblastlike cells from both men and women [5][6][7], specific androgen receptors can be identified by nuclear and cytosolic binding assays (Table 1). Similarly, osteoblasts obtained from fresh femoral bone specimens can also metabolize the circulating androgen androstenedione to testosterone and 5␣-dihydrotestosterone (DHT) in both men and women [8] at rates dependent mainly on androstenedione concentration. Cells of osteoclast lineage may also have these properties, though this is less well established. Androgen receptors have also been directly demonstrated in osteoblasts and osteocytes around the growth plate [9]. Androgens may promote proliferation and differentiation of osteoblasts, inhibit osteoclast recruitment or affect osteoblast-to-osteoclast signaling.Animal studies have mostly been performed in orchiectomized (orch) male rats, though there are reservations about the appropriateness of this model because the rat skeleton grows throughout life. Replacement therapy with either testosterone or 5␣-DHT results in enhanced bone mass, though this remains lower than in control rats [10].In male humans, androgens have a marked effect on bone growth and peak bone mass via the growth hormone/ IGF-I axis; accordingly, androgen deficiency before puberty leads to lower bone mineral density (BMD) in both cortical and trabecular bone. Loss of androgens in later life is associated with increased bone resorption and loss of trabecular bone, but cortical bone mass is not greatly affected [11,12]. In a study of 12 men who had undergone judicial castration for ''sexual delinquency'' [13], bone turnover was increased and lumbar spine BMD fell significantly, with evidence of the most rapid loss in the first 5 years after castration. Rates of bone loss were as high as 7% per year, comparable to loss rates seen in early postmenopausal women. In this study, calcitonin therapy was effective in reducing bone loss, and low calcitonin levels have been reported in another group of young hypogonadal men who had not undergone surgery [14]. Others have found low plasma 1,25 dihydroxyvitamin D levels and impaired calcium absorption in hypogonadal men [15].This combination o...

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Does Hypogonadism Contribute to the Occurrence of a Minimal Trauma Hip Fracture in Elderly Men?

Cited by 242 publications

References 40 publications

Preoperative Supraphysiological Testosterone in Older Men Undergoing Knee Replacement Surgery

Preoperative Supraphysiological Testosterone in Older Men Undergoing Knee Replacement Surgery

Regulation of interleukin-6, osteoclastogenesis, and bone mass by androgens. The role of the androgen receptor.

Sex Hormones and Osteoporosis in Men

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