Low bone mass: assessing absolute fracture risk and the need to treat younger postmenopausal women.
Abstract: The need to initiate treatment for a postmenopausal woman with a low bone mass should be based on that individual's fracture risk over a finite period of time. Fracture assessment tools, such as the recently introduced FRAXTM model, allows the clinician to estimate an individual's absolute fracture risk over the next decade of their life. Such estimates are particularly useful for younger postmenopausal females with bone density values in the osteopenic range. Fracture risk increases with age and is inversely related to bone mineral density values. A history of previous fracture after the age of 45 and within 10 years of assessment increases subsequent fracture risk.
Subject: Fractures (Care and treatment)
Postmenopausal women (Care and treatment)
Bones (Density)
Author: Honig, Stephen
Pub Date: 07/01/2009
Publication: Name: Bulletin of the NYU Hospital for Joint Diseases Publisher: J. Michael Ryan Publishing Co. Audience: Academic Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2009 J. Michael Ryan Publishing Co. ISSN: 1936-9719
Issue: Date: July, 2009 Source Volume: 67 Source Issue: 3
Accession Number: 247340116
Full Text: Bone loss in women increases significantly during the late perimenopausal period and may reach more than 2% annually in the early postmenopausal period, particularly in the more hormonally sensitive lumbar spine (trabecular bone). Femoral (cortical) bone loss is more linear and is influenced by aging and estrogen deprivation. Women who enter menopause with a low bone mass are at increased risk for osteoporosis and fractures in the decade after menopause. The most common fracture that occurs in the first decade of menopause involves the distal forearm and results from an increased incidence of falls sustained by women during that period of time. Such fractures, particularly in women with low bone mass, are likely a marker for women at increased risk for subsequent fractures. A 50-year-old woman with a normal bone density has a 10-year fracture risk of about 6%, a figure that doubles for females of that age with bone density scores in the osteoporotic range. Women who are at the onset of menopause with normal bone density values have a low 10-year fracture risk. Over a lifetime, postmenopausal bone loss averages about 1% a year. Such progressive age-related bone loss increases fracture risk. In general, healthy women with no fracture history are at low fracture risk during the first decade of menopause, unless they enter the menopausal transition with a relatively low bone mass. Attention should be paid to balance issues and falls prevention for all postmenopausal women as part of a comprehensive fracture reduction strategy.

The decision to initiate bone-strengthening medication for a postmenopausal woman with a low bone mass should be based on that individual's absolute fracture risk. Recently introduced fracture assessment tools allow clinicians to provide patients with an estimate of their fracture risk over a finite period of time. In defining such fracture risks, it is important to be cognizant of population-based fracture rates among postmenopausal women with normal bone density scores in order to compare the increased risk to age-related normative values. Fragility or osteoporotic fractures increase with age, as older bones are more likely to be less dense and to exhibit microarchitectural changes, such as microcracks that are associated with such fractures. Many women undergo bone density testing at the time of the menopausal transition and are concerned about their bone health and fracture risk. Fortunately, there have been a series of clinical studies that have reported on serial bone density tests and fracture rates during the first decade of menopause, and this data allows us to understand rates of bone loss and fracture rates in the younger postmenopausal population. Such information also allows the clinician to identify those women in the first decade of menopause who are at enough increased risk to warrant starting bone-strengthening treatment. The data also helps us to assure most women in their fifties that they do not need immediate treatment, as their finite time-related fracture risk is low. Bone loss, however, is progressive, and many such women will require active treatment as they age beyond the first decade of menopause.

Peak Bone Mass and Bone Loss in the First Decade of Menopause

Women accrue their greatest amount of bone, or peak bone mass, generally, between 20 to 25 years of age. This maximum of bone mass is mainly under genetic control. Women with eating disorders, low body weight with secondary amenorrhea, sedentary habits, and other lifestyle factors may fail to reach their full genetic potential for bone growth and have lower bone masses than their age-related peers. (1) About 15% of women aged 30 to 40 will have bone density scores in the osteopenic range and about 3% will have osteoporotic range scores, most commonly in the lumbar spine. (2) Over a normal life span, untreated females will lose, on average, about 35% of their cortical bone and 50% of their trabecular bone. (3) On an individual basis, however, there is considerable variation of bone loss rates, with some women experiencing rapid bone loss and others little or no bone loss. Postmenopausal bone loss is influenced by genetic and environmental factors, especially low body mass index. (4,5) Postmenopausal bone loss is usually progressive, although recent data suggests that 9% of older women have stable bone densities and that this subset of women have fewer fractures and live longer than their age-matched peers, with either expected or increased rates of bone loss. (6) Understanding rates of bone loss and short-term fracture risk is critical to defining when and if younger postmenopausal females need to begin bone strengthening therapies.

Zhai and colleagues investigated the natural history of postmenopausal bone loss among almost 1000 Caucasian females from Chingford in the United Kingdom who had at least two bone density tests over a 15-year period. They found that bone loss from the femoral neck was linear over time and averaged 1.67% annually, while lumbar spine bone loss was significantly greater during the early postmenopausal years and then slowed with increasing age. (7) In the American observational multi-site investigation, the Study of Women's Health Across the Nation (SWAN), which involves females of different ethnic groups, Finkelstein and coworkers detailed rates of bone loss from the pre- or early perimenopause through the first few years of postmenopause. Investigators found that bone density changed very little during pre- or early perimenopause, but, instead, declined more significantly during late perimenopause. Through the early postmenopausal years, annual rates of bone loss averaged 1.8% to 2.3% in the spine and 1.0% to 1.4% in the hip, with rates of bone loss being faster among those in the lowest tertile of body weight. They also determined that ethnic differences in rates of bone loss were largely eliminated when differences in body weight were controlled. (8) A prospective study of bone loss in menopausal Australian women, conducted by Guthrie and associates, involved 224 females aged 46 to 59 years, who each underwent two bone density studies, an average of 24 months apart. The women who became menopausal during the study had more bone loss at the hip and spine than those who had become menopausal several years earlier (Table 1). The most significant bone loss was seen at both the hip and lumbar spine in the months immediately following the final menstrual period. (9)

Fracture Rates in the First Decade of Menopause

Fracture rates are inversely related to bone density scores and are highest among women with osteoporosis. However, the greatest number of fractures occurs in the numerically much larger group of women with osteopenia. (10) It is estimated there are about 8 million postmenopausal American women with osteoporosis and as many as three-times that number with osteopenia. (11) Identifying those subjects at increased short- and intermediate-term risk of fractures, who may need immediate bone strengthening treatment, is important in order to reduce the incidence of fractures in high risk younger postmenopausal women. Conversely, women at lower fracture risk during the first decade of menopause can be reassured that they do not require immediate pharmacologic intervention. A 50-year-old Caucasian female has a greater than 50% risk of sustaining a fracture during the remainder of her life time. (12) In the first decade of menopause, the greatest number of fractures involves the distal forearm, while hip and vertebral fractures occur with increasing frequency in the later postmenopausal years (Table 2). (13) The 10-year probability of a 50-year-old woman with a normal bone density sustaining a fracture is about 6%. (14) Recently, there have been a number of studies that have reported on the incidence of fractures and rates of bone loss in younger postmenopausal females, and this data further defines fracture risks and fracture sites for this population.

The Danish Osteoporosis Prevention Study included 872 women (50.7 [+ or -] 2.9 years of age), who were not taking hormone replacement therapy during early menopause, and were prospectively followed for 10 years. The outcome measures of this study included a bone density-based diagnosis of osteoporosis of the femoral neck or spine at 10 years and a history of fracture during that decade, or either alone. There were 78 fractures (9% of the population) sustained during the 10 years, over 80% of which involved the distal forearm. Those women who fractured had normal but significantly lower bone density scores at study entry than did the women who did not fracture. Women with study entry T scores of greater than -1.4 of either the spine or femoral neck had less than a 10% risk of developing osteoporosis or sustaining a fracture during the first decade of menopause. Thirty-eight percent of women who were osteopenic at study entry progressed to the development of osteoporosis at the end of the 10-year period. (15)

The National Osteoporosis Risk Assessment (NORA) study is an American population-based study involving over 200,000 postmenopausal females, almost 71,000 of whom were between 50 to 59 years of age at study entry. NORA was designed to study the relationship between bone mineral density (at a peripheral site) and fractures at 1 and 3 years after study entry. About 5% of the younger women had a peripheral bone mineral density in the osteoporotic range at study entry. The first-year fracture rate among the younger postmenopausal women was about 1%. (16) Women with a history of a previous wrist fracture after age 45 had three-times the risk of sustaining a fracture than did women without such a fracture history. (17) Women in the NORA study with self-reported poor health and lower bone density scores at study entry were at increased short-term fracture risk. (18)

Clinical Decisions in the First Decade of Menopause

Bone loss and fracture rates, both among postmenopausal women with normal as well as lower bone mineral density scores, help frame the absolute risk for fractures that women in the first decade of menopause face. It is clear that the younger postmenopausal women with a history of a prior fracture in the decade preceding menopause are at higher risk than their aged-matched peers with no fracture history. The decision to recommend bone-strengthening medication to all postmenopausal women regardless of age should be based on their absolute fracture risk, and this is particularly so in the younger women who are likely to be at less risk for short and intermediate-term fracture risk. The World Health Organization's FRAXTM assessment model provides 10-year fracture risks based on a number of individual variables, including body mass index, age, smoking and alcohol intake history, current use of corticosteroids, parental hip fracture history, prior fracture history, and hip bone density scores. The computer-generated program, which is based on past data provided by a large number of international population-based studies, estimates an individual's 10-year risk of a hip and a major osteoporotic fracture.

For American women with an absolute risk exceeding 3% (hip) or 20% (major), bone-strengthening treatment is suggested. Such fracture assessment tools help women understand their risk in simple mathematical terms and reassure both the clinician and patient that the decision to treat or not to start treatment is rooted in a risk assessment. It is important to emphasize that the 1 -year risk is always the lowest risk period and that deferring the start of treatment for several years may be prudent for those with borderline 10-year risk profiles. A healthy 51 -year-old postmenopausal, nonsmoking woman with no previous fracture and a femoral neck T score of -2.2 would have an 8.5% 10-year risk of a major osteoporotic fracture. This static measure does not include rates of bone loss, which may confer additional, increased risk; such a patient should be followed closely with serial bone density tests and measures of bone turnover.

High levels of such markers may influence the decision to recommend treatment, particularly if they are reflected by significant declines in bone density. (19) It is also important to remember that the incidence of fractures is directly related to an increase in the rates of falling among women, which begins as early as perimenopause when estrogen levels start to decline. (20)

Conclusions

The decision to initiate treatment in females during the first decade of menopause should be based on absolute fracture risk over a finite period of time and on the need to preserve or increase a low bone mass. It is generally agreed that postmenopausal women with osteoporotic T scores should be treated, but the type of drug and the length of time it should be used will depend on an individual's risk factors, particularly bone mineral density, prior fracture history, and general health. Healthy, younger postmenopausal women with only minimal or moderately decreased bone mass and no fracture history are unlikely to need treatment during the first decade of menopause. A falls prevention strategy, including balance training, should be part of a comprehensive fracture reduction program, particularly for those individuals with a history of falls and balance problems. It is important to emphasize the need for adequate amounts of dietary and supplemental calcium and vitamin D, as well as to encourage patients to engage in regular weightbearing exercises as ways to help maintain healthy and strong bones.

Disclosure Statement

The author has no financial or proprietary interest in the subject matter or materials discussed, including, but not limited to, employment, consultancies, stock ownership, honoraria, and paid expert testimony.

References

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(2.) Kanis JA. Osteoporosis III: Diagnosis of osteoporosis and assessment of fracture risk. Lancet. 2002;359:1929-36.

(3.) Riggs BK, Wahner HW, Seeman E, et al. Changes in bone mineral density of the proximal femur and spine with aging; differences between the postmenopausal and senile osteoporosis syndromes. J Clin Invest. 1982;70:716-23.

(4.) Riis BJ, Hansen MA, Jensen AM, et al. Low bone mass and fast rate of bone loss at menopause: equal risk factors for future fracture: a 15-year follow-up study. Bone. 1996;19:9-12.

(5.) Makovey J, Nguyen TV, Naganathan V, et al. Genetic effects on bone loss in peri- and postmenopausal women: a longitudinal twin study. J Bone Miner Res. 2007;11:1773-80.

(6.) Cauley JA, Lui-L-Y, Barnes D, et al. Successful skeletal aging: a marker of low fracture risk and longevity. The Study of Osteoporotic Fractures. J Bone Miner Res. 2009;24:134-43.

(7.) Zhai G, Hart DJ, Valdes AM, et al. Natural history and risk factors for bone loss in postmenopausal women: a 15-year followup population-based study. Osteoporos Int. 2008;19:1211-17.

(8.) Fikelstein JS, Brocckwell SE, Mehta V, et al. Bone mineral density changes during the menopause transition in a multiethnic cohort of women. J Clin Endocrinol Metab. 2008;93:861-68.

(9.) Guthrie JR, Ebeling PR, Hopper JL, et al. A prospective study of bone loss in menopausal Australian-born women. Osteoporos Int. 1998;8:282-9.

(10.) Siris E, Miller PD, Barrett-Connor E, et al. Identification and fracture outcomes of undiagnosed low bone mineral density in postmenopausal women. Results from National Osteoporosis Risk Assessment. JAMA. 2001;286:2815-22.

(11.) National Osteoporosis Foundation. America's Bone Health: The State of Osteoporosis and Low Bone Mass in Our Nation. Washington, DC: National Osteoporosis Foundation, 2002.

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(15.) Abrahamsen B, Rejnmark L, Nielsen SP, et al. Ten-year prediction of osteoporosis from baseline bone mineral density: development of prognostic thresholds in healthy postmenopausal women. The Danish Osteoporosis Study. Osteoporos Int. 2006;17:245-51.

(16.) Siris E, Brenneman SK, Miller PD, et al. Predictive value of low BMD for 1-year fracture outcomes is similar for postmenopausal women ages 50-64 and 65 and older. Results from the national osteoporosis Risk Assessment (NORA). J Bone Miner Res. 2004;19:1215-20.

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(18.) Chen Y-T, Miller PD, Barrett-Connor E, et al. An approach for identifying postmenopausal women age 50-64 at increased short-term risk for osteoporotic fracture. Osteoporos Int. 2007;18:1287-96.

(19.) Hough S. Fast and slow bone losers. Relevance to the management of osteoporosis. Drugs Aging. 1998;12(Suppl):1-7.

(20.) Davies JC, Manning DP, Kemp GJ, et al. The rising number of underfoot accidents after the menopause causing both fracture and non-fracture injuries. QJM. 2001;94:699-707.

Correspondence: Stephen Honig, M.D., Osteoporosis Center. 301 East 17th Street, NYU Hospital for Joint Diseases, New York, New York 10003; stephen.honig@nyumc.org.

Stephen Honig, M.D., M.Sc., is Clinical Associate Professor, New York University School of Medicine, and Director of The Osteoporosis Center, Division of Rheumatology, Department of Medicine, NYU Hospital for Joint Diseases, NYU Langone Medical Center, New York, New York.
Table 1 Mean Annual Percentage Changes in Lumbar Spine and Femoral
Neck Bone Mineral Density, by Menopausal Transition Group

Menopausal Transition Group       N    LS BMD (% Change/Year)

Remained premenopausal           31          0.31 (0.34)
Pre- to early perimenopausal     36         -0.13 (0.30)
Remained early perimenopausal    33         -0.20 (0.27)
Became late perimenopausal       22         -0.92 (0.42)
Became postmenopausal            42         -2.48 (0.24)
Remained Postmenopausal          60         -0.74 (0.21)

Menopausal Transition Group          P       FN BMD (% Change/Year)

Remained premenopausal              0.4           0.72 (0.44)
Pre- to early perimenopausal        0.7           0.52 (0.31)
Remained early perimenopausal       0.3           0.08 (0.44)
Became late perimenopausal         0.07           -0.71 (0.64)
Became postmenopausal            < 0.0005         -1.74 (0.23)
Remained Postmenopausal           < 0.005         -0.50 (0.28)

Menopausal Transition Group         P

Remained premenopausal             0.1
Pre- to early perimenopausal       0.1
Remained early perimenopausal      0.9
Became late perimenopausal         0.3
Became postmenopausal            < 0.0005
Remained Postmenopausal            0.08

(Adapted from Table 4, Guthrie JR, Ebeling PR Hopper JL, et al. (9)
[c] International Osteoporosis Foundation and National Osteoporosis
Foundation, Springer London. With kind permission from Springer
Science+Business Media.)

Table 2 Estimated Incident Fractures for Females by Fracture Type,
Age, and Race in the USA (2005)

                    Number of Fractures by
                   Fracture Type in Females

Stratum           Hip    Vertebral     Pelvis

Age
  50-64        13,420      57,562     136,624
  65-74        25,288      85,020      88,072
  75-84        84,274     142,892      70,317
  > 85         99,771     103,156      31,815

Race
  White       201,123     347,739     285,973
  Black         6,995      13,838      15,030
  Hispanic      8,175      15,417      15,045
  Other         6,460      11,636      10,781
Total         222,753     388,630     326,828

                   Number of Fractures by
                  Fracture Type in Females

Stratum         Wrist       Other       Total

Age
  50-64         5,532     159,043     372,180
  65-74        15,596      84,963     299,938
  75-84        43,059     105,394     445,937
  > 85         38,469      65,576     338,788

Race
  White        88,973     366,360   1,290,168
  Black         5,004      18,057      58,923
  Hispanic      5,276      17,755      61,668
  Other         3,403      12,805      45,085
Total         102,655     414,976   1,455,843

(Reproduced from J Bone Miner Res 2007;22;465-75 with permission of
the American Society for Bone and Mineral Research.)
Gale Copyright: Copyright 2009 Gale, Cengage Learning. All rights reserved.