OSTEOPOROSIS

 Health Evidence Bulletins - Wales

Systematic literature search to December 2000 plus some key references from 20

6: Primary and Secondary Prevention of Osteoporosis in Men

The World Health Organisation criteria for osteoporosis and osteopenia were developed for women but can appropriately be applied to meni,ii. A review of recent evidence concluded that the relationship between BMD and hip fracture risk was similar in men and women although the data are scanty. It was recommended that the same diagnostic thresholds be used in men – namely a BMD at the hip that lies 2.5 SD of more below the reference range for young women – until further research changes this viewi. Another recent study found that, there is a different relationship between bone density and fracture in the two sexes, but that the current WHO definition of osteoporosis in postmenopausal women can be appropriately applied to meni,ii.
i. Kanis JA, Gluer CC. An update on the diagnosis and assessment of osteoporosis with densitometry. Osteoporosis International 2000; 11: 192-202
(Type V evidence – expert opinion based on a review of the literature)
ii. Selby PL, Davies M, Adams JE. Do men and women fracture bones at similar bone densities? Osteoporosis International 2000; 11(2): 153-157
(Type V evidence – expert opinion based on an examination of the relationship between bone density and vertebral fracture in 37 men (mean age 55) and 264 women (mean age 64) attending for assessment of possible osteoporosis)
See Chapter 1 for risk/prevention factors
  • Exercise
  • Calcium and vitamin D
  • Calcitonin
  • Bisphosphonates
  • Testosterone
  • Parathyroid hormone
  • Monofluorophosphate
6a. Site-specific exercise may help improve and maintain BMD at the femur, lumbar and os calcis sites in older men. When BMD sites were specific to the sites loaded during exercise, increases of ca 2.6% (2.1% in the exercisers and –0.5% in the controls) were foundi.
(Health gain notation – 4 "unknown")
However, the biological importance of the small changes observed from most outcomes, quality of studies, and limited data pool prevent any firm conclusions. A need exists for further studies i.

A systematic review of the effect of exercise for the prevention of low bone mass in young males is underway ii. A systematic review is in progress to evaluate the effectiveness of exercise therapy (with or without additional supplements or therapy) in the prevention and treatment of osteoporosis in meniii.

 i. Kelley GA, Kelley KS, Tran ZV. Exercise and bone mineral density in men: a meta-analysis. Journal of Applied Physiology 2000; 88(5): 1730-1736
(Type I evidence – systematic review (literature search completed December 1998) and meta-analysis of 8 studies, 26 effect sizes and 225 subjects)

ii. Kemper HCG, Bakker I, van Tulder MW, Kostense PJ, Courteix D. Exercise for preventing low bone mass in young males and females (Protocol). Cochrane Database of Systematic Reviews. Cochrane Library 2001, Issue 4
(Type I evidence - systematic review of randomised and non-randomised controlled trials of healthy males and females, aged 6-35 years, in progress)

iii. See Tai S, Parsons T, Rutherford O, Illiffe S. Physical activity for preventing and treating osteoporosis in men. [Protocol] Cochrane Database of Systematic Reviews. Cochrane Library 2001, Issue 4
(Type I evidence - systematic review including adult males, in progress)
6b. A calcium supplement of 750 mg/day prevents loss of BMD, reduces femoral medullary expansion, secondary hyperparathyroidism, and high bone turnover. A supplement of 15 micrograms/day vitamin D3 is less effective, and because its effects are seen only at low calcium intakes, suggests that its beneficial effect is to reverse calcium insufficiencyi.
See statement 1.2e concerning the recommended daily calcium intakes for men.		 i. Peacock M, Liu G, Carey M et al. Effect of calcium or 250H vitamin D3 dietary supplementation on bone loss at the hip in men and women over the age of 60. Journal of Clinical Endocrinology & Metabolism 2000; 85(9): 3011-3019
(Type II evidence – 4 year randomised controlled trial of 316 women (mean age 73.7 years) and 122 men (mean age 75.9 years). Subjects were randomised to 750 mg calcium or 15 micrograms 250H vitamin D3)

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6c. Uncertainty remains about the efficacy of regimens which include vitamin D or its analogues in fracture prevention in elderly men and women with involutional or post-menopausal osteoporosis Particularly if co-supplementation is required, significant cost differences are likely to exist between regimens. Further randomised controlled trials are currently being conducted to clarify the effectiveness of community fracture prevention programmes employing vitamin D supplementationi.
(Health gain notation - 4 "unknown")		 i. Gillespie WJ, Avenell A, Henry DA, O’Connell DL, Robertson J. Vitamin D and Vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis. [updated 12 November 2000]. Cochrane Database of Systematic Reviews. Cochrane Library 2001, Issue 4
http://www.update-software.com/
abstracts/ab000227.htm
 [accessed 29.11.01]
(Type I evidence - systematic review and meta-analysis of 14 quasi- randomised and controlled trials, 7220 elderly men and women; 25% of the patients were lost to follow-up)
6d. Calcitonin See statement 4.2a.
6e. In men with osteoporosis, alendronate significantly increases spine, hip and total-body BMD and helps prevent vertebral fractures and decreases in height. The men who received alendronate had a mean (±SE) increase in BMD of 7.1±0.3% at the lumbar spine, 2.5±0.4% at the femoral neck, and 2.0±0.2% for the total body (p<0.001 for all comparisons with base-line). Men who received placebo had an increase in lumbar spine BMD of 1.8±0.5% (p<0.001 in comparison with base-line) but no significant changes in femoral neck or total-body BMD. The incidence of vertebral fractures was lower in the alendronate group (0.8% versus 7.1%, p=0.02) as was the decrease in height (0.6 mm versus 2.4 mm, p=0.02). Alendronate was generally well toleratedi.
(Health gain notation - 2 "likely to be beneficial")		 i. Orwoll E, Ettinger M, Weiss S et al. Alendronate for the treatment of osteoporosis in men. New England Journal of Medicine 2000; 343(9): 604-610
(Type II evidence – two year randomised controlled trial of 10 mg alendronate or placebo, given daily, on BMD in 241 men (aged 31-87 years, mean 63) with osteoporosis. All subjects received 500 mg/d calcium and 400-450 IU/d vitamin D)
6f. Observational studies in men with idiopathic and secondary osteoporosis suggest that intermittent cyclic etidronate therapy increases bone density at the lumbar spine by 5-10%, with smaller increases at the hip. It would therefore appear that cyclical etidronate has comparable effects on bone density in men and women, but the effect on fracture incidence in men has not been established.i i. Anonymous. Osteoporosis. Clinical Guidelines for Prevention and Treatment. Update on pharmacological interventions and an algorithm for management. London: Royal College of Physicians, 2000
(Type V evidence – expert opinion based on a systematic review of the literature and quoting Francis RM. Cyclical etidronate in the management of osteoporosis in men. Reviews in Contemporary Pharmacotherapy 1998; 9: 261-266)

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6g. Testosterone therapy is a promising treatment for eugonadal men with osteoporosis. In one study, lumbar spine BMD increased by 5% over six monthsi.
In another study, testosterone therapy in eugonadal men with acquired hypogonadism, decreased subcutaneous fat and increased lean muscle mass. It also reduced bone remodelling and increased trabecular bone density. During therapy spinal BMD and trabecular BMD increased by 5%±1% (p<0.001) and 14%±3% (p<0.001) respectively. Radial BMD did not changeii.		 i. Anderson FH, Francis RM, Peaston RT, Wastell HJ. Androgen supplementation in eugonadal men with osteoporosis: Effects of 6 months treatment on markers of bone formation and resorption. Journal of Bone and Mineral Research 1997; 12: 472-478
(Type IV evidence – observational study of 21 men aged 34-73 (mean 58) with osteoporotic crush fracture, treated with intramuscular testosterone esters (Sustanon 250) every 2 weeks for 6 months)

ii. Katznelson L, Finkelstein JS, Schoenfeld DA, Rosenthal DI, Anderson DJ, Klibanski A. Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism. Journal of Clinical Endocrinology and Metabolism 1996; 81(12): 4358-4365
(Type IV evidence – 18 month longitudinal study of testosterone therapy in 29 adult men with acquired hypogonadism (aged 22-69 years, median 58 years). There was some drop out from the study (n=23 at 18 months) and the analysis was based on the subjects remaining rather than by intention-to-treat. Baseline data for 36 eugonadal men were also compared with 44 age-matched eugonadal controls)

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6h. A pilot study suggested that parathyroid hormone (PTH) is associated with substantial increases in lumbar spine and hip bone density in men with idiopathic osteoporosis i.
Caveat: A very small study with BMD rather than fracture reduction as the primary endpoint.		 i. Kurland ES, Cosman F, McMahon DJ, Rosen CJ, Lindsay R, Bilezikian JP. Parathyroid hormone as a therapy for idiopathic osteoporosis in men: effects on bone minueral density and bone markers. Journal of Clinical Endocrinology & Metabolism 2000; 85(9): 3069-3076
(Type II evidence – 18 month randomised controlled trial of 23 men, 30-86 years old, randomised to 400 IU PTH-(1-34) or vehicle received by daily sc injection. All men received 1,500 mg calcium and 400 IU vitamin D daily)
6i. Early treatment of idiopathic osteoporosis in the male using a fluoride-calcium regimen can improve cancellous and cortical bone density, reduce the incidence of vertebral fractures and attenuate back pain. Three patients (10%) in the treatment group suffered a total of four vertebral fractures versus 12 patients (40%) with 17 fractures in the control group (p=0.001). All side effects of therapy were mild and transienti. i. Ringe JD, Dorst A, Kipshoven C, Rovati LC, Setnikar I. Avoidance of vertebral fractures in men with idiopathic osteoporosis by a three year therapy with calcium and low-dose intermittent monofluorophosphate. Osteoporosis International 1998; 8: 47-52
(Type II evidence – randomised controlled trial of 64 men with osteoporosis (mean age 53 years), and no previous vertebral fracture, assigned to intermittent (three months on, one month off) treatment with monofluorophosphate (114 mg/day) plus continuous calcium supplementation (900-1000 mg/day) or 1000 mg/day calcium alone. 60 men who attended the first control visit were included in an intention-to-treat analysis)
6j. Consensus guidelines are available for the management of male osteoporosisi.
Caveat: These guidelines were completed in 1997 and are likely to be out of date in many respects.		 i. Eastell R, Boyle IT, Compston J et al. Management of male osteoporosis: report of the UK consensus group. QJM 1998; 91: 71-92
(Type V evidence – expert consensus guidelines)

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Health Evidence Bulletins: Wales, Duthie Library, UWCM, Cardiff CF14 4XN. e-mail: weightmanal@cardiff.ac.uk