OSTEOPOROSIS

Health Evidence Bulletins - Wales (logo)

Systematic literature search to December 2000 plus some key references from 2001

1: Epidemiology, Risk Factors and Prevention

This bulletin is a supplement to, not a substitute for, professional skills and experience. Users are advised to consult the supporting evidence for a consideration of all the implications of a recommendation
The Statements The Evidence
1.1 Prevalence
1.1a. The World Health Organisation estimated the prevalence of osteoporosis in western women (adjusted to 1990 US white women) at any site as 14.8% in women aged 50-59, 21.6% for ages 60-69, 38.5% for ages 70-79, rising to 70.0% in women aged 80 or morei.

The likelihood that any individual will suffer from an osteoporotic fracture is relatively high. At a conservative estimate, more than one-third of adult women will sustain one or more osteoporotic fractures in their lifetime. The lifetime risk of symptomatic fracture for a 50 year old white woman in the UK has been estimated as 13% for the forearm, 11% for the vertebrae and 14% for the femoral neck. Corresponding figures for 50 year old men are 2%, 2% and 3%ii. The lifetime risk of hip fracture was estimated as 15.6-17.5% in white women and 5.2-6.0% in white meni.

i. World Health Organisation. Assessment of Fracture Risk and its Application to Screening for Postmenopausal Osteoporosis. WHO Technical Report Series 843. Geneva: WHO, 1994
(Type V evidence – expert consensus opinion based on a review of the literature)

ii. Anonymous. Osteoporosis. Clinical Guidelines for Prevention and Treatment. London: Royal College of Physicians, 1999
http://www.doh.gov.uk/osteorep.htm
[accessed 29.11.01]
(Type V evidence – expert opinion based on a systematic review of the literature and quoting several studies including: Cooper C. Epidemiology and definition of osteoporosis in Compston JE, ed. Osteoporosis: New Perspectives on Causes, Prevention and Treatment. London: Royal College of Physicians, 1996; and Dolan P, Torgerson DJ. The cost of treating osteoporotic fractures in the United Kingdom female population. Osteoporosis International 1998; 8(6): 611-617)

1.2 Risk and Preventive Factors
1.2a. A four year longitudinal study of 800 elderly women and men showed that risk factors consistently associated with bone loss in elders included female sex, thinness, and weight loss, while weight gain appeared to protect against bone loss for both men and womeni.

A larger risk factor study identified seven variables: age, BMD T-score, fracture after age 50 years, maternal hip fracture after age 50, weight less than or equal to 125 lbs (57 kg), smoking status and use of arms to get up from a chairii.

i. Hannan MT, Felson DT, Dawson-Hughes B et al. Risk factors for longitudinal bone loss in elderly men and women: the Framingham Osteoporosis Study. Journal of Bone and Mineral Research 2000; 15(4): 710-720
(Type IV evidence – 4-year study of 800 men and women, 69% of the original cohort of 1164. Mean age at baseline = 74±4.5 years (age range, 67-90 years). A large variation in BMD measurements across different bone sites was noted)
ii.
Black DM, Steinbuch M, Palermo L et al. An assessment tool for predicting fracture risk in postmenopausal women. Osteoporosis International 2001; 12: 519-528
(Type IV evidence – assessment tool using data from the five-year Study of Osteoporotic Fractures (SOF). 7782 women aged 65 or older (mean age 73.3 years) with BMD measurements and base-line risk factors included in the analysis)

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1.2b. Thinness is an important risk factor for low bone mass. Women in the lowest tertiles of percentage of body fat or BMI in the placebo group had up to 12% lower BMD at baseline and a more than 2-fold higher 2-year bone loss as compared with women in the highest tertiles (p=0.004) i. (See also Statement 1.2a) i. Ravn P, Cizza G, Bjarnason NH et al. Early Postmenopausal Intervention Cohort (EPIC) Study Group. Low body mass index is an important risk factor for low bone mass and increased bone loss in early postmenopausal women. Journal of Bone and Mineral Research 1999; 14(9): 1622-1627
(Type IV evidence – observations of data from the placebo group, N=417, of a study of alendronate treatment in recently postmenopausal women with normal bone mass)
1.2c. Smoking is associated with lower BMD and increased fracture risk in postmenopausal but not in premenopausal women. In postmenopausal women, bone loss was greater in current smokers than non-smokers, bone density diminishing by about an additional 2% for every 10 year increase in age, with a difference of 6% at age 80. In current smokers relative to non-smokers, the risk of hip fracture was similar at age 50 but greater thereafter by an estimated 17% at age 60, 41% at 70, 71% at 80 and 108% at 90i. . (See also Statement 1.2a)

Evidence concerning men is limited. Results from the Framingham Osteoporosis Study (21 men) suggested that current smoking is associated with bone loss. Over a 4-year period, men who were current smokers lost more BMD at the trochanter site than men who never smoked (a –4% change compared with a +0.7% change in BMD, p=0.02)ii.

A case-control study of men with vertebral fractures suggested a significantly increased risk of these fractures in current smokers (odds ratio, OR=2.8, 95% CI 1.2-6.7) which was not observed in ex smokers (OR=1.6, 95% CI 0.7-3.6)iii. These results are consistent with an earlier case-control studyiv.

Two studies suggested that the effects of smoking and low BMI are additive, particularly for postmenopausal womenv,vi.

In one small study, early postmenopausal women with a low Body Mass Index (BMI) had a lower bone mineral density (BMD) and an increased rate of loss of BMD. On average, women in the lowest tertile of BMI had a 10% lower BMD compared with those in the highest tertile. Smoking is associated with a 4% lower BMD compared to non smokers. There was, on average, a 14% difference in BMD between the extremes of thin, smoking women and heavy, non-smoking womenv.

A much larger study of more recently menopausal women (adjusted for coffee and alcohol intake) found smaller differences. The differences in BMD between current smokers and never smokers were 1.6, 2.9 and 1.9% respectively for lumbar spine, femoral neck and total body. A statistical interaction was found between smoking and fat mass, indicating that women in the highest tertile of fat mass were unaffected by cigarette smokingvi.

i. Law MR, Hackshaw AK. A meta-analysis of cigarette smoking, bone mineral density and risk of hip fracture: recognition of a major effect. British Medical Journal 1997; 315(7112): 841-846
http://www.bmj.com/cgi/content/
full/315/7112/841

[accessed 29.11.01]
(Type IV evidence – meta-analysis of 29 cross-sectional studies (reporting BMD difference in 2156 smokers and 9705 non-smokers) and 19 cohort and case-control studies (recording 3889 hip fractures); Commentary in Shin KR. Review: smoking is associated with decreased bone mineral density and increased risk of hip fracture in postmenopausal women. Evidence Based Nursing 1998; 1(3): 88)

ii. Hannan MT, Felson DT, Dawson-Hughes B et al. Risk factors for longitudinal bone loss in elderly men and women: the Framingham Osteoporosis Study. Journal of Bone and Mineral Research 2000; 15(4): 710-720
(Type IV evidence – 4-year study of 800 men and women, 69% of the original cohort of 1164. Mean age at baseline = 74±4.5 years (age range, 67-90 years). A large variation in BMD measurements across different bone sites was noted)

iii. Scane AC, Francis RM, Sutcliffe AM, Francis SJD, Rawlings DJ, Chapple CL. Case-control study of the pathogenesis and sequelae of symptomatic vertebral fractures in men. Osteoporosis International 1999; 9: 91-97
(Type IV evidence – case-control study of 91 men with symptomatic vertebral fractures (median age 64 years, range 27-79 years) compared with 91 age-matched controls. 56% of the vertebral fracture patients had osteoporosis (lumbar spine BMD T-score = 2.5))

iv. Seeman E, Melton LJ, O’Fallon WM, Riggs BL. Risk factors for spinal osteoporosis in men. American Journal of Medicine 1983; 75: 977-983
(Type IV evidence – case-control study of 105 consecutive male patients with vertebral fracture (mean age 64.7 years, range 44-85) with osteoporosis or osteopenia, compared with 105 age-matched men with Paget’s disease attending the same clinic)

v. Bjarnason NH, Christiansen C. The influence of thinness and smoking on bone loss and response to hormone replacement therapy in early postmenopausal women. Journal of Clinical Endocrinology and Metabolism 2000; 85(2): 590-596
(Type IV evidence – Baseline and placebo subgroup analysis of data from a randomised controlled trial of 153 early postmenopausal (1-6 years) women comparing treatments of 1 or 2 mg estradiol with placebo)

vi. AP, Brot C, Gram J, Kolthoff N, Mosekilde L. Premenopausal smoking and bone density in 2015 perimenopausal women. Journal of Bone and Mineral Research 2000; 15(4): 780-787
(Type IV evidence – Baseline observations from 2015 recently menopausal (0-2 years, aged 45-58 years) and hysterectomized (and <52 years old) women from a national cohort study, the Danish Osteoporosis Prevention Study)

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1.2d. Corticosteroid use can induce osteoporosisi,ii,iii,iv. For users of oral corticosteroids the relative rate of fracture during treatment, after adjusting for confounding variables, was: nonvertebral fracture, RR = 1.33 (95% CI 1.29-1.38); hip fracture = 1.61 (95% CI 1.47-1.76); forearm fracture = 1.09 (95% CI 1.01-1.17); and vertebral fracture = 2.60 (95% CI 2.31-2.92)ii.

Patients taking higher doses (at least 7.5 mg daily of prednisolone or equivalent) had significantly increased risk of non-vertebral fracture (RR=1.44, 95% CI 1.34-1.54), hip fracture (RR=2.21, 95% CI 1.85-2.64) and vertebral fracture (RR=2.83, 95% CI 2.35-2.40) relative to patients using oral corticosteroids at lower doses (less than 2.5 mg daily)iii.

According to the General Practice Research Database (for England and Wales) in 1997, at any point in time, oral corticosteroids were being used by 0.9% of the total adult population. The overall use of bone-active medication for this group was low (between 4.0% and 5.5%). The authors concluded that the current population in the UK at risk of developing corticosteroid induced osteoporosis might be as large as 350,000iv. See also statements on osteoporosis following transplantation and osteoporosis in children ( Chapters 5 & 7).

i. Adinoff AD, Hollister MD. Steroid-induced fractures and bone loss in patients with asthma. New England Journal of Medicine 1983; 309(5): 265-268
(Type IV evidence – hospital record review of 128 patients)
ii. van Staa TP, Leufkens HGM, Abenhaim L, Zhang B, Cooper C. Use of oral corticosteroids and risk of fractures. Journal of Bone and Mineral Research 2000; 15(6): 993-1000
iii. van Staa TP, Leufkens HGM, Abenhaim L, Zhang B, Cooper C. Oral corticosteroids and fracture risk: relationship to daily and cumulative doses. Rheumatology 2000; 39: 1383-1389
(ii & iii. Type IV evidence – cohort study in the UK, using data from the General Practice Research Database for England and Wales. 244,235 oral corticosteroid users and 244,235 controls, aged 18 and over, matched by age, sex and medical practice)
iv. van Staa TP, Leufkens HG, Abenhaim L, Begaud B, Zhang B, Cooper C. Use of oral corticosteroids in the United Kingdom. QJM 2000; 93(2): 105-111
(Type IV evidence – Information from 683 practices contained in the General Practice Research Database for England and Wales)

 

1.2e. There is a positive association between calcium intake and bone mass. All but two of 52 investigator controlled intervention studies gave positive results for bone mass. Of 86 observational studies, 64 found a significant positive association between calcium intake and bone mass, bone loss or fracture risk. One found a positive effect in men only, 19 found no effect and two found a negative effect (in one of which the authors suspected confounding variables as the explanation). The authors concluded that it seemed prudent to accompany regimens directed at increasing bone mass (for all age groups) with a calcium intake in the range of 40-60 mmol/day (1600-2400 mg/day) i.
Recommendations from the National Osteoporosis Society (NOS) and a subgroup of the Committee on Medical Aspects of Food and Nutrition Policy (COMA) for daily calcium intakes (reference nutrient intakes) in normal healthy individuals are ii,iii.
Children aged 0-12 months 525 mg/d
Children aged 1-3 years 350 mg/d
Children aged 4-6 years 450 mg/d
Children aged 7-10 years 550 mg/d
Males aged 11-18 years 1000 mg/d
Females aged 11-18 years 800 mg/d
Males & Females aged 19-65+ years 700 mg/d
During pregnancy RNI for age
During lactation + 550 mg/d*

*Recent evidence suggests that this additional increment may not be necessaryii.

Practical recommendations for ensuring adequate intake of calcium are also providedii,iii. Over 2000-2500 mg/day may pose a risk in relation to formation of kidney stones or other problems. These recommendations are of particular relevance to individuals who have or are at risk from, osteoporosisii.

The National Diet and Nutrition Survey found that children between the ages of 11-14 and 15-18 years were not reaching the current reference nutrient intake (RNI) for calcium, and intakes of sodium (a potential confounding factor for bone health when in excess) were generally twice that of the RNIiii. Another review concluded that those at greatest risk of low calcium intake are young women (aged 16-18) and elderly women who are not living in institutionsiv.

i. Heaney RP. Calcium, dairy products and osteoporosis. Journal of the American College of Nutrition 2000; 19(2): 83S-99S
(Type V evidence – detailed review, possibly systematic but no search methodology given, of 86 observational studies and 52 investigator-controlled calcium intervention studies)

ii. National Osteoporosis Society. Information Sheet on Calcium Rich Foods and Bone Health. London: National Osteoporosis Society, July 2001
(Type V evidence – expert opinion and guidelines)
Available from the National Osteoporosis Society, PO Box 10, Radstock, Bath BA3 3YB (tel. 01761 471771)

iii. National Dairy Council. Diet and Bone Health, Topical Update. November 1999. London: National Dairy Council, 1999
(Type V evidence – expert opinion and guidelines.
Derived from: Department of Health. Report on Health and Social Subjects 41. Dietary Reference Values for Food, Energy and Nutrients for the United Kingdom. London: Department of Health, 1991)

iv. Gregory J, Lowe S. National Diet and Nutrition Survey: Diets of British Schoolchildren aged 4-18 years. Vol.1. Report of the National Diet and Nutrition Survey. London: The Stationery Office, 2000
http://www.foodstandards.gov.uk/news/
pressreleases/nationaldiet

[accessed 29.11.01]
(Type IV evidence – survey carried out, January – December 1997, of a representative sample of 2672 young people aged 4-18 years)

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1.2f. In elderly women, low fractional calcium absorption in the setting of low calcium intake increases the risk for hip fracture. After adjustment for age, women with a dietary calcium intake of <400 mg/d calcium had a relative risk (RR) of 1.60 (95% CI 1.16-2.19) per one SD (7.7%) decrease in fractional calcium absorption, while those with a dietary intake of =400 mg/d had an RR of 1.10 (95% CI 0.90-1.36). Women with low calcium absorption and low calcium intake were at greatest risk for subsequent hip fracture. In women whose dietary calcium intake was at least 400mg/d, decreased fractional calcium absorption was not associated with risk for hip fracture, regardless of supplemental vitamin D use i.

An adequate dietary calcium intake and a physically active lifestyle in late decades of life could translate into a reduction in the risk of osteoporosis. Women in the top tertile of quadriceps strength (=23 kg) and dietary calcium intake (=710mg/day) had a 15% higher BMD than those in the lowest tertiles (=15kg and =465 mg/day). The difference was comparable in men (11%). Among subjects with the lowest tertiles of BMI (=23 kg/m2 for women and =24 kg/m2 for men), quadriceps strength (=15 kg for women and =28 kg for men) and dietary calcium intake (=465 mg/day) 64% of women and 40% of men were classified as having osteoporosis according to WHO criteriaii.

i. Ensrud KE, Duong T, Cauley JA et al. Study of Osteoporotic Fractures Research Group. Low fractional calcium absorption increases the risk for hip fracture in women with low calcium intake. Annals of Internal Medicine 2000; 132(5): 345-353
(Type IV evidence – prospective cohort study, for an average of 4-8 years, of 5452 nonblack women, 69+ years of age, participating in the fourth examination of the Study of Osteoporotic Fractures. Fractures were recorded in women with a calcium intake of <400 mg/d, in women with =400 mg/d and also in those with or without supplementary calcium)

ii. Nguyen TV, Center JR, Eisman JA. Osteoporosis in elderly men and women: effects of dietary calcium, physical activity, and body mass index. Journal of Bone and Mineral Research 2000; 15(2): 322-331
(Type IV evidence – cross-sectional epidemiological study, in Australia, of 1075 women and 690 men aged 69±6.7 years. Smoking status, a potential confounder, was not considered)

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1.2g. Of the few stronger-evidence studies of dairy foods and bone health, most had outcomes that were not significant. However, white women <30 years old are most likely to benefit. There are too few studies in males and minority ethnic groups to determine whether dairy foods promote bone healthi. i. Weinsier RL, Krumdieck CL. Dairy foods and bone health: Examination of the evidence. American Journal of Clinical Nutrition 2000; 72(3): 681-689
(Type I evidence – systematic review of 46 studies (and 57 separate outcomes) including 12 randomised controlled trials)
1.2h. A deficiency of protein will contribute to bone loss. It is also suggested that an excess may affect the body’s ability to absorb calcium, but this is currently the subject of much debate. COMA recommends that adults should avoid any intake of twice the Reference Nutrient Intake (ie 1.5g per kg of body weight per day)i. i. National Dairy Council. Diet and Bone Health, Topical Update. November 1999 London: National Dairy Council, 1999
(Type V evidence – expert opinion and guidelines.
Derived from: Department of Health. Report on Health and Social Subjects 41. Dietary Reference Values for Food, Energy and Nutrients for the United Kingdom. London: Department of Health, 1991)
1.2i. The main sources of vitamin D are by cutaneous synthesis from ultraviolet radiation and, in the diet, from fatty fishes, fish liver oil and, to a lesser extent, eggsi. The recommended daily intakes of vitamin D for young adults were quoted as 100 to 200 IUi,ii, 400 IU for those aged 51-70 and 800 IU for people over 70 years of agei. There is evidence that some younger, as well as older people are at risk of vitamin D insufficiencyi. The European population may be at risk because of the high latitude and a low nutritional supply of vitamin Di. There is, however, no established evidence to support the administration of vitamin D supplements to healthy children, adolescents, and premenopausal womenii.

A subgroup of the Committee on Medical Aspects of Food and Nutrition Policy (COMA) recommendations for reference nutrient intakes (RNI) of vitamin D in normal healthy individuals are: 0-6 months, 8.5 microg/day; 7-12 months & 1-3 years, 7 microg/day; 65+ years, during pregnancy and lactation, 10 microg/day. No RNI is set between 4 and 64 years. It is assumed that skin synthesis will ensure adequate Vitamin D status provided that there is regular exposure to summer sunlightiii.

Combined calcium and vitamin D have been shown to have a protective effect against fractures in elderly people (see Statement 4.3a).

i. Meunier PJ. Calcium, vitamin D and vitamin K in the prevention of fractures due to osteoporosis. Osteoporosis International 1999; 9(suppl.2): S48-S52
(Type V evidence – expert opinion)

ii. Kaufman JM. Role of calcium and vitamin D in the prevention and the treatment of postmenopausal osteoporosis: an overview. Clinical Rheumatology 1995; 14(suppl.3): 9-13
(Type V evidence – expert opinion)

iii. National Dairy Council. Diet and Bone Health, Topical Update. November 1999. London: National Dairy Council, 1999
(Type V evidence – expert opinion and guidelines. Derived from: Department of Health. Report on Health and Social Subjects 41. Dietary Reference Values for Food, Energy and Nutrients for the United Kingdom. London: Department of Health, 1991)

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1.2j. From one small study, the desirable levels of vitamin D (25(OH)D) for children were estimated at between 12 and 20 ng/ml. 31% of 51 normal children studied in winter had levels below 12 ng/ml and 80% had levels below 20 ng/ml. Since cutaneous synthesis of vitamin D is rather limited in winter, oral vitamin D supplementation might be considered. However, this relationship between subclinical vitamin D deficiency in children and long-term risk remains speculative and a longitudinal study would be requiredi.

The National Diet and Nutrition Survey found that children aged 15-18 had poor vitamin D status ii.

Some elderly people living in institutions would benefit from an improvement in vitamin D statusiii.

i. Docio S, Riancho JA, Perez A, Olmos JM, Amado JA, Gonzalez-Macias J. Seasonal deficiency of vitamin D in children: a potential target for osteoporosis-preventing strategies? Journal of Bone and Mineral Research 1998; 13(4): 544-548
(Type IV evidence – vitamin D metabolite and parathyroid hormone (PTH) serum level measurements in 21 children (aged 9±1 years) in March and October, prior to and after the administration of a daily supplement of 25(OH)D, 40 microgr for 7 consecutive days. Plus a cross-sectional study of summer/winter vitamin D levels in 94 children (aged 8±2 years). The study was carried out in a cloudy region in Northern Spain)
ii. Gregory J, Lowe S. National Diet and Nutrition Survey: Diets of British Schoolchildren aged 4-18 years. Vol.1. Report of the National Diet and Nutrition Survey. London: The Stationery Office, 2000
http://www.foodstandards.gov.uk/news/
pressreleases/nationaldiet

[accessed 29.11.01]
(Type IV evidence – survey carried out, January – December 1997, of a representative sample of 2672 young people aged 4-18 years)
iii. National Dairy Council. Diet and Bone Health, Topical Update. November 1999 London: National Dairy Council, 1999
(Type V evidence – expert opinion and guidelines)

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1.2k. There is some preliminary evidence of a positive association between fruit and vegetable consumption and bone health in middle-aged womeni,ii. There was a significant difference in lumbar spine BMD between the lowest and highest quartiles of intake of zinc, magnesium, potassium, fibre and vitamin Ci . A further, small, study provided additional support for a link between BMD and magnesium & potassium consumptionii. i. New SA, Bolton-Smith C, Grubb DA, Reid DM. Nutritional influences on bone mineral density: a cross-sectional study in premenopausal women. American Journal of Clinical Nutrition 1997; 65: 1831-1839
(Type IV evidence – cross-sectional study, by questionnaire, of 1230 eligible healthy female volunteers (aged 45-49 years) to the osteoporosis screening programme. Response rate = 82% (n=994))
ii. New SA, Robins SP, Campbell MK et al. Dietary influences on bone mass and bone metabolism: further evidence of a positive link between fruit and vegetable consumption and bone health. American Journal of Clinical Nutrition 2000; 7: 142-151
(Type IV evidence – cross-sectional study, by questionnaire, of 62 healthy women aged 45-55 years)
1.2l. An intake of vitamin K >105 mg/d may decrease the risk of hip fracture in women. Women in quintiles 2-5 of vitamin K intake had a significantly lower age-adjusted relative risk (0.70, 95% CI 0.53-0.93) of hip fracture than women in the lowest quintile (<109 microgram/day). Risk of hip fracture was also inversely associated with lettuce consumption, the food that contributed most to dietary vitamin K intake (RR: 0.55, 95% CI 0.40-0.78 for one or more servings per day compared with one or fewer servings per week)i. i. Feskanich D, Weber P, Willett WC, Rockett H, Booth SL, Colditz CA. Vitamin K intake and hip fractures in women: a prospective study. American Journal of Clinical Nutrition 1999; 69(1): 74-79
(Type IV evidence – prospective analysis by questionnaire of the diet of 72,327 women aged 38-63 years and 10 year follow-up of 270 hip fractures resulting from low or moderate trauma)
1.2m. Habitual intakes of caffeine from the equivalent of four or more cups of coffee per day may be associated with decreased bone density, yearly losses of as much as 0.5% total body calcium and as much as a doubling of the hip fracture risk. There is evidence that this can be reduced or eliminated by adequate calcium intakei. i. Harris SS. Effects of caffeine consumption on hip fracture, bone density and calcium retention. In Nutritional Aspects of Osteoporosis (ed. B Dawson-Hughes, RP Heaney). SA Publication. New York: Springer Verlag, 1998
(Type V evidence – expert opinion based on a review of the literature including 5 prospective controlled studies looking at the link between caffeine consumption and fracture risk)
1.2n. In teenage girls, carbonated beverage consumption and bone fractures are associated (odds ratio, OR=3.14; 95% CI 1.45-6.78, p=0.04). Among physically active girls, the cola beverages, in particular, are highly associated with bone fractures (OR=4.94; 95% CI 1.79-13.62, p=0.002). The mechanism of this effect has not been fully exploredi.
Caveats: Since the design of this study was cross-sectional rather than longitudinal, causation couldn’t be inferred. The fracture information was self-reported. BMD measurements were not made and calcium consumption was not assessed.
i. Wyshak G. Teenaged girls’ carbonated beverage consumption and bone fractures. Archives of Pediatric and Adolescent Medicine 2000; 154(6): 610-613
(Type IV evidence – cross-sectional (retrospective) study in the US, by self-administered questionnaire, of 460 9th and 10th grade high-school girls.)

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1.2o. Two observational studies suggest that modest alcohol intake (approximately 3-4 units per week in one study of premenopausal womeni) can have a positive role in bone healthi,ii.
(Health Gain Notation – 2 "likely to be beneficial")
However, excessive alcohol consumption increases bone loss and risk of fractures, particularly in menii,iii.
(Health Gain Notation – 6 "likely to be harmful")

One unit of alcohol = One glass of wine or one single spirits or a half pint of beer

 

i. New SA, Bolton-Smith C, Grubb DA, Reid DM. Nutritional influences on bone mineral density: a cross-sectional study in premenopausal women. American Journal of Clinical Nutrition 1997; 65: 1831-1839
(Type IV evidence – cross-sectional study, by questionnaire, of 1230 eligible healthy female volunteers (aged 45-49 years) to the osteoporosis screening programme. Response rate = 82% (n=994))
ii. Scane AC, Francis RM, Sutcliffe AM, Francis SJD, Rawlings DJ, Chapple CL. Case-control study of the pathogenesis and sequelae of symptomatic vertebral fractures in men. Osteoporosis International 1999; 9: 91-97
(Type IV evidence – case-control study of 91 men with symptomatic vertebral fractures (median age 64 years, range 27-79 years) compared with 91 age-matched controls. 56% of the vertebral fracture patients had osteoporosis (lumbar spine BMD T-score = 2.5))
iii. National Osteoporosis Society. Diet and Bone Health. London: National Osteoporosis Society, 1999. pp. 8-9
(Type V evidence – expert opinion and guidelines)
Available from the National Osteoporosis Society, PO Box 10, Radstock, Bath BA3 3YB (tel. 01761 471771)
1.2p. For the generally healthy person there is no sound evidence that the consumption of salt at the present average level of 9g/day constitutes a risk factor for osteoporosis i.
There is, however, some evidence that dietary salt intake affects urinary calcium excretionii.
i. Cohen AJ, Roe FJC. Review of risk factors for osteoporosis with particular reference to a possible aetiological role of dietary salt. Food & Chemical Toxicology 2000; 38(2-3): 237-253
(Type V evidence – well referenced non-systematic review of animal, clinical and epidemiological studies)
ii. Antonios TFT, MacGregor GA. Salt – more adverse effects. Lancet 1996; 348: 250-251
(Type V evidence – expert opinion based on non-systematic review of the literature)

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1.2q. Long term exposure to fluoridated drinking water does not increase the risk of fracture. In women with continuous exposure to fluoride for 20 years compared to no exposure, the risk of hip fracture was slightly reduced (risk ratio, RR=0.69, 95% CI 0.50-0.96) as was the risk of vertebral fracture (RR=0.73, 95% CI 0.55-0.97). There was a non-significant trend towards an increased risk of wrist fracture (RR=1.32, 95% CI 1.00-1.71) and no difference in the risk of humerus fracture (RR=0.85, 95% CI 0.58-1.23) i. i. Phipps KR, Orwoll ES, Mason JD, Cauley JA. Community water fluoridation, bone mineral density, and fractures: prospective study of effects in older women. British Medical Journal 2000; 321: 860-864
http://www.bmj.com/cgi/content
/full/321/7265/860

[accessed 29.11.01]
(Type IV evidence – prospective study of fracture rate (average follow-up of 7.0 years) of women with continuous exposure to fluoridated drinking water during the past 20 years (n=3218) and those with no exposure (n=2563). Measurements were adjusted for known confounders)
1.2r. A three year prospective population study of 25,000 subjects in the UK to examine the relationship between life style and bone mass (as measured by calcaneal ultrasound) and subsequent fracture (in particular, hip fracture) end points is almost completei.

An analysis of results from the EPIC study suggested that high-impact physical activity is associated with ultrasound attenuation by the heel bone and, by extrapolation, to a reduced fracture risk, in men and women. Men who reported participating in = 2 hours/week high impact activity had 8.44 dB/MHz (95% CI, 4.49-12.40) or 9.5% higher ultrasound attenuation than men who reported no activity of this type. In women, the difference in ultrasound attenuation between those reporting any high impact activity and those reporting none was 2.41 dB/MHz (0.45-4.37) or 3.4% higher. Moderate impact activity had no effect. However, climbing stairs was strongly independently associated with ultrasound attenuation in women (0.64 dB/MHz (0.19-1.09) for each additional five flights of stairs). There was a significant negative association in women between time spent watching television or video and heel bone ultrasound attenuation, which decreased by 0.08 dB/MHz (0.02-0.14) for each additional hour of viewing per weekii.

A five year study in Canada (the Canadian Multicentre Osteoporosis Study, CaMos) looking at many environmental risk factors (sociodemographic, medical history, diet, physical activity and family history) is underway and due for completion in 2002iii.

There does, however, appear to be a threshold of intensity over which a negative impact on bone occurs, particularly when the exercise is of an anaerobic nature or occurring in thin, amenorrheic participantsiv. The female athlete triad is a serious syndrome comprising three interrelated components: (1) Disordered eating; (2) Amenorrhaea; and (3) Osteoporosisv.

A large study looking at vertebral deformityvi,vii found that very heavy levels of physical activity* in all three age groups were associated with an increased risk of vertebral deformity in men (odds ratio, age adjusted, OR=1.5-1.7, with all 95% confidence intervals excluding unity). No increased risk was seen in women. Current walking or cycling for more than ½ hour/day was associated with a reduced risk of vertebral deformity in women (OR=0.8, 95% CI 0.7-1.0)vii.
[*A very heavy level of physical activity was defined in this study as those activities involving continouous heavy work such as agricultural or construction work, or professional sports involvement]
Caveat: Vertebral deformity may not be a good marker for osteoporosis. Large variations were found between sites and increased vertebral deformity was found in younger men (the authors concluded that this may have been related to trauma early in adult life). No direct comparison of vertebral deformity and BMD was made in the European Vertebral Osteoporosis Study (EVOS) although research was cited in which a correlation had been found.

i. Department of Health (PRP) Policy Research Program. Dietary & other determinants of bone health and fracture in men & women: A prospective population based study. National Research Register Project No. M0005037420 (end date 30.9.00)
http://www.update-software.com/
National/nrr-frame.html

[accessed 29.11.01]
(Type IV evidence – prospective population study of 25,000 men & women aged 45-74 years resident in East Anglia with extensive data collection at baseline (repeated 7-day diaries, food frequency questionnaires and biological samples))
ii. Jakes R, Khaw K-T, Day NE et al. Patterns of physical activity and ultrasound attenuation by heel bone among Norfolk cohort of European Prospective Investigation of Cancer (EPIC Norfolk): population based study. British Medical Journal 2001; 322: 1-5
http://www.bmj.com/cgi/content
/full/322/7279/140

[accessed 29.11.01]
(Type IV evidence – cross-sectional population based study of 2296 men and 2914 women participating in EPIC Norfolk)
iii. Tenenhouse A, Kreiger N, Hanley D. Canadian Multicentre Osteoporosis Study (CaMos). Drug Development Research 2000; 49(3): 201-205
(Type IV evidence – prospective population study of 9423 randomly selected subjects aged 25 years or more to assess the relationship between low-trauma fractures, bone characteristics and risk factors)
iv. Cromer B, Harel Z. Adolescents: At increased for osteoporosis? Clinical Pediatrics 2000; 39: 565-574
(Type V evidence – expert opinion)
v. West RV. The female athlete. The triad of disordered eating, amenorrhoea and osteoporosis. Sports Medicine 1998; 26(2): 63-71
(Type V evidence – expert opinion)
vi. O’Neill TW, Felsenberg D, Varlow J, Cooper C, Janis JA, Silman AJ. The prevalence of vertebral deformity in European men and women: The European Vertebral Osteoporosis Study. Journal of Bone and Mineral Research 1996; 11(7): 1010-1018
(Type IV evidence – European wide, age stratified, cross-sectional population based study of 15,570 males and females aged 50-79 years (mean age=64.1 years) in 36 centres. The EVOS study. Median response rate for participation = 54% (range 5-83%). A limited survey of 40 non-responders from 20 centres suggested no evidence of important bias in relation to the key variables tested but this cannot be excluded. The nature of the population sampling frames varied from Centre to Centre and this could be part of the explanation for the large variations in the prevalence of vertebral deformities from Country to County and Centre to Centre. For example, the UK prevalence in Bath was half that in Aberdeen.)
vii. Silman AJ, O’Neill TW, Cooper C, Kanis J, Felsenberg D. Influence of physical activity on vertebral deformity in men and women: Results from the European Vertebral Osteoporosis Study. Journal of Bone and Mineral Research 1997; 12(5): 813-819
(Type IV evidence – Data from 30 centres in the EVOS study and 14,261 subjects. 12,568 subjects without vertebral deformities acted as controls to 1693 subjects with vertebral deformities)

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1.2s. Women in the highest quintile of menarch (age = 16 years) were found to have an increased risk of vertebral deformity (OR=1.48, 95% CI 1.16-1.88). Increased menopausal age (>52.5 years) was associated with a reduced risk of deformity (OR=0.78, 95% CI 0.60-1.00), while use of the contraceptive pill was also protective (OR=0.76, 95% CI 0.58-0.99). There were no apparent effects of parity or breast feeding i.
Caveat: Vertebral deformity may not be a good marker for osteoporosis (see statement 1.2t).
i. O’Neill TW, Silman AJ, Naves Diaz MN, Cooper C, Kanis J, Felsenberg D. The European Vertebral Osteoporosis Study. Influence of hormonal and reproductive factors on the risk of vertebral deformity in European women. Osteoporosis International 1997; 7: 72-78
(Type IV evidence – cross-sectional survey of women within the EVOS study -7,530 women from 30 centres. 6646 women without vertebral deformities acted as controls to 884 subjects with vertebral deformities)
1.2t. A maternal history of hip fracture was found to double the risk of hip fracture (relative risk = 2.0, 95% CI 1.4-2.9). The authors also concluded that women with multiple risk factors and low bone density have an especially high risk of hip fracture. Maintaining body weight, walking for exercise, avoiding long-acting benzodiazepines, minimizing caffeine intake, and treating impaired visual function are among the steps that may decrease the riski.

A maternal history of hip fracture is associated with a modest increased risk of vertebral deformity in men (odds ratio, OR=1.3, 95% CI 1.0-1.8). The risk being greater in those aged 65 years and over (OR=1.5, 95% CI 1.0-2.4) and in those from low prevalence areas. There was no increased risk in womenii.
Caveat: Vertebral deformity may not be a good marker for osteoporosis (see statement 1.2r).

i. Cummings SR, Nevitt MC, Browner WS et al. for the Study of Osteoporotic Fractures Research Group. Risk factors for hip fracture in white women. New England Journal of Medicine 1995; 332: 767-773
(Type IV evidence – longitudinal study of 9516 white women aged 65 years or more, with no previous hip fracture, followed up for an average of 4.1 years)
ii. Diaz MN, O’Neill TW, Silman AJ; The European Vertebral Osteoporosis Study Group. The influence of family history of hip fracture on the risk of vertebral deformity in men and women. Bone 1997; 20(2): 145-149
(Type IV evidence – Data from 12,816 men and women in the EVOS study. Estimates of exposure were based on subjects’ recall only)

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1.2u. Up to 50% of patients with apparently well treated coeliac disease may have osteoporosis, with 20% of patients increasing their lifetime fracture risk five foldi. i. Coeliac Disease Resource Centre. Coeliac Disease and Osteoporosis. Trowbridge: CDRC, June 1999
http://www.cdrc.org.uk
[accessed 29.11.01]
(Type V evidence – expert opinion)
1.2v. Women with the Estrogen Receptor (ER) PvuII genotypes PP and Pp may have a greater risk of relatively fast bone loss after menopause than those with the pp genotype. There was no association between the ER genotype and BMD at baseline. In the non-HRT group the lumbar spine BMD decreased more in subjects with the ER genotypes PP (6.4%) and Pp (5.2%) than in subjects with the pp genotype (2.9%) (p=0.002). In the HRT group, the relative changes were similar in all three ER genotype groups. Thus, women with the PP and Pp genotype may preferentially derive benefit from hormone replacement therapy (HRT)i.

There is approximately 2% difference in the BMD at the hip, spine and radius, between homozygous BsmI or TaqI vitamin-D receptor genotypesii.

Apolipoprotein E genotype does not modify lumbar or femoral neck BMDs or serum bone biochemical markers or their response to hormone replacement therapy in early postmenopausal Caucasian womeniii.

The ss and Ss genotypes (type 1 collagen) were found to be over-represented in patients with severe osteoporosis and vertebral fractures (54%) compared with controls (27%). This is equivalent to a relative risk of 2.97 (95% CI 1.63-9.56) for vertebral fracture in individuals who carry the ‘s’ alleleiv.

i. Salmén T, Heikkinen A-M, Mahonen A et al. Early postmenopausal bone loss is associated with PvuII estrogen receptor gene polymorphism in Finnish women: Effect of hormone replacement therapy. Journal of Bone and Mineral Research 2000; 15(2): 315-321
(Type IV – study of the influence of ER genotype on BMD before and after a five-year randomised controlled trial of hormone replacement therapy in 322 early postmenopausal women from Finland)

ii. Cooper GS, Umbach DM. Are vitamin D receptor polymorphisms associated with bone mineral density? A meta-analysis. Journal of Bone and Mineral Research 1996; 11: 1841-1849
(Type IV evidence – meta-analysis of observational studies)

iii. Heikkinen AM, Kroger H, Niskanen L et al. Does apolipoprotein E genotype relate to BMD and bone markers in postmenopausal women? Maturitas 2000; 34(1): 33-41
(Type IV evidence – study of the relationship of apolipoprotein E genotype to BMD and bone biochemical markers in 464 early postmenopausal women and 5-year follow-up of BMD changes with and without HRT)

iv. Grant SFA, Reid DM, Blake G, Herd R, Fogelman I, Ralston SH. Reduced bone density and osteoporosis associated with a polymorphic Sp1 binding site in the collagen type I a 1 gene. Nature Genetics 1996; 14: 203-205
(Type IV evidence – cross sectional study of 205 women in Aberdeen and 94 women in London. The Aberdeen cohort (aged 61.3±0.74) were recruited from consecutive clinic referrals (52.6%) and the remainder drawn at random from the general population. The London cohort were 94 healthy volunteers who had attended for bone screening)

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1.2w. BMD predicts the risk of breast cancer in older women. The risk of breast cancer was about 30% to 50% higher per 1 SD increase in BMD. The age-adjusted incidence rate of breast cancer per 1000 person-years among women in the lowest quartile of distal radius BMD was 2.46 compared with 5.99 among women with the highest quartile. The authors concluded that these results are consistent with the hypothesis that long-term exposure to estrogen in women as measured by BMD is an important risk factor for breast cancer, but it is possible that this reflects other hormonal factorsi.

In another study, after adjusting for the effects of lifetime ovulation and body mass index, each 0.1g/cm2 increase in lumbar spine and femoral neck BMD was associated with a 2.1-fold (95% CI 1.3-3.4) and 1.5-fold (95% CI 1.0-2.4) respectively, higher risk of breast cancerii. Adjustment for other confounders did not alter the result. The authors estimated that estrogen therapy in osteoporotic women, even if raising the risk of breast cancer by 70%, as suggested in some studies, would not elevate their risk to the level experienced by their non-osteoporotic counterpartsii.

Women in the highest quartile of bone mass are at greater risk for postmenopausal breast cancer than those in the lowest quartile. After adjustments for age and other potential confounders, the rate ratios for the risk of breast cancer were 1.0, 1.3, 1.3 and 3.5 from the lowest quartile to the highest (p for trend, <0.001). The mechanisms underlying this relation are not understood, but the roles of estrogens and/or endogenous androgens have also been considerediii.

i. Cauley JA, Lucas FL, Kuller LH, Vogt MT, Browner WS, Cummings SR. Bone mineral density and risk of breast cancer in older women. Journal of the American Medical Association 1996; 17: 1404-1408
(Type IV evidence – case control study of 97 breast cancer patients within a cohort including 6757 controls. Participants were volunteers, rather than a representative sample, but age-adjusted incidence rates of breast cancer were comparable. HRT users were excluded from the study)

ii. Nguyen TV, Center JR, Eisman JA. Association between breast cancer and bone mineral density: the Dubbo Osteoporosis Epidemiology Study. Maturitas 2000; 36: 27-34
(Type IV evidence – nested case-control study involving 30 breast cancer cases and 120 controls, aged 68±6 (mean±SD), as part of the Dubbo Osteoporosis Study)

iii. Zhang Y, Kiel DP, Kreger BE et al. Bone mass and risk of breast cancer among postmenopausal women. New England Journal of Medicine 1997; 336(9): 611-617
(Type IV evidence – The Framingham Study. A cohort of 1373 women (aged 47-80 years old) recruited between 1967 to 1970 and followed by biennial examination until the end of 1993)

1.2x. Congenital hip dysplasia (CHD) was associated with a 6.3-fold increased risk for low BMD at the hip. The authors concluded that a history of conservatively treated CHD may be a major risk factor for low BMD at the hip in about 1 out of 10 women. Further prospective studies would be required to find out if this translates into an increased risk of hip fracturei. i. Obermayer-Pietsch BM, Walter D, Kotschan S, Freigassner-Pritz M, Windhager R, Leb G. Congenital hip dysplasia and bone mineral density of the hip – a new risk factor for osteoporotic fracture? Journal of Bone and Mineral Research 2000; 15(9): 1678-1682
(Type IV evidence – prospective evaluation of 240 premenopausal women (33±7 years). 31 women reported a history of conservatively treated CHD, 4 had undergone surgery; the remaining women in the group acted as controls)

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1.2y. There is fair evidence to support the position that low-dose oral contraceptive use has a favourable effect on BMD. Of 13 studies summarised in a systematic review, nine showed a positive effect, four did not show an association but none showed a BMD decrease i. i. Kuohung W, Borgatta L, Stubblefield P. Low dose oral contraceptives and bone mineral density: an evidence-based analysis. Contraception 2000; 61(2): 77-82
(Type II/III evidence – systematic review of intervention and observational studies, via Medline and reference list searches, of 13 studies of women using low-dose oral contraceptives (20-40 m g ethinyl estradiol) that measured BMD by bone densitometry. Only one tiny randomised controlled trial (n=17) was included)
1.2z. The results of a large observational study, and the secondary analysis of a randomised controlled trial, suggest that the use of statins at dosages prescribed in clinical practice is not associated with a reduction in the risk of fracturei,ii. It is suggested that the lower hip fracture rates previously reported among statin users may be explained by the residual confounding effect of obesityi.

A meta-analysis suggested that long-term anticoagulant treatment is associated with no more than a modest increase in osteoporotic fracture risk. Bone density was significantly decreased among exposed subjects in the ultradistal radius (standardised mean difference, -0.39, 95% CI –0.67 to –0.10) but not in the distal radius, lumbar spine, femoral neck or femoral trochanter. This should be verified in future longitudinal studiesiii.

i. van Staa T-P, Wegman S, de Fries F, Leufkens B, Cooper C. Use of statins and risk of fractures. Journal of the American Medical Association 2001; 285(14): 1850-1855
(Type IV evidence – case-control study of data from the UK General Practice Research Database. Cases were 81,880 fracture patients, aged 50 or older, paried with 81,880 age-, sex- and practice-matched controls)

ii. Reid IR, Hague W, Emberson J et al, on behalf of the LIPID Study Group. Effect of pravastatin on frequency of fracture in the LIPID study: secondary analysis of a randomised controlled trial. Lancet 2001; 357: 509-512
(Type II/IV evidence – analysis of adverse event reports from a six-year randomised controlled trial of pravastatin or placebo in 9014 patients (17% women, median age 62 years))

iii. Caraballo PJ, Gabriel SE, Castro MR, Atkinson EJ, Melton LJ, 3rd. Changes in bone density after exposure to oral anticoagulants: a meta-analysis. Osteoporosis International 1999; 9(5): 441-448
(Type IV evidence – systematic review of 9 cross-sectional studies)

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