Assessment and Management ofPostmenopausal Osteoporosis in China

Assessment and Management of Postmenopausal Osteoporosis in China

Jie Wu, Qinjie Tian

Department of Obstetrics and Gynecology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Peking Union Medical College Hospital

, Peking Union Medical College, Beijing, China

Considering the aging population, longer life expectancy, and many dramatic changes in people’s lifestyles during recent years in China, although the prevalence of postmenopausal osteoporosis in China remains lower than that of other industrialized countries, future studies are needed and more effort should be made to increase Chinese people’s awareness regarding osteoporosis and to promote good bone health.

Key Words: China, Osteoporosis

Received: February 26, 2010 Revised: March 4, 2010 Accepted: March 24, 2010

Corresponding Author: Qinjie Tian, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, 100730, P.R.

China

E-mail: [email protected]

Osteoporosis is defined as a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in fragility of bone and susceptibility to risk of fracture

. Osteoporosis can be divided into either primary or secondary osteoporosis. Primary osteoporosis is usually due to bone loss that occurs in both sexes at all ages, but often follows menopause in women which be called postmenopausal osteoporosis. In contrast, secondary osteoporosis is a result of medications (eg, glucocorticoids), other conditions (eg, hypogonadism), or diseases (eg, malabsorption). Bone strength primarily reflects the integration of bone density and bone quality. Bone density is expressed as grams of mineral per area or volume, and in any given individual is determined by peak bone mass and amount of bone loss. Bone quality refers to architecture, turnover,

damage accumulation, and mineralization

, which are difficult or impossible to measure in clinical practice at this time. Currently bone mineral density (BMD) is the most commonly measured

, and it accounts for approximately 70% of bone strength. The World Health Organization (WHO) defines osteoporosis in postmeno- pausal women over age 50 as BMD T-score less than or equal to 2.5 SDs below the mean at the total hip, femoral neck, or lumbar spine

.

Osteoporosis can be diagnosed clinically by BMD, however, the presence of a fragility fracture constitutes a clinical diagnosis of osteoporosis. According to a report, osteoporosis is responsible for an estimated 90%

of all hip and spine fractures in white American women ages 65 to 84

. Approximately 25% of women require long-term care after a hip fracture, and 50%

will have some long-term loss of mobility. Hip fracture

has a profound impact on quality of life, as evidenced

by findings that 80% of women older than 75 years

preferred death to a bad hip fracture resulting in their

placement in a nursing home. In addition, osteoporosis

has financial, physical, and psychosocial consequences,

all of which significantly affect the individual, the

family, and the community.

The aging of the population and lifestyle changes make postmenopausal osteoporosis a major public health problem throughout the world, not only in North America and Europe, but also in developing countries such as China. And it has received great attention in industrialized countries. In the United States, osteoporo- sis affects approximately ten million Americans; and more than 34 million have low bone mass

. However, limited research is reported in many developing countries including China, where aging and changing lifestyles likely contribute to increased osteoporosis, and the prevalence may continue to increase in the near future. One recent study reported that the average prevalence of osteoporosis in Chinese adults aged 50 years and over was 22.4% in men and 44.1% in women, which was much higher than the overall prevalence (13%)

. In order to reduce the prevalence of postmenopausal osteoporosis and osteoporotic fractures, assessment of osteoporosis risk factors and management strategies, including lifestyle changes and, if indicated, medical treatments are needed.

RISK FACTORS OF

OSTMENOPAUSAL OSTEOPOROSIS

1. Menopause and age factors

Women experience more rapid bone loss in the early years following menopause, which places them at earlier risk for fractures. In adult women, bone mineral density changes little until the onset of menopause when estrogen levels decline. Postmenopausal women continue to lose bone mass obviously. Bone loss begins to accelerate approximately 2 to 3 years before the last menses, and this acceleration ends 3 to 4 years after menopause. Generally, postmenopausal women lose 2～

3% of bone annually in the first few years. Afterward, bone loss slows to about 1% to 1.5% per year

. Although some of the decline can be attributed to age- related factors, lower estrogen levels were implicated as

the cause for approximately two thirds of the bone loss.

Lower estrogen levels have also been significantly associated with increased fracture risk in older women

.

Age is also a strong risk factor for osteoporosis and osteoporotic fracture, particularly hip fracture. Based on BMD alone, it would be expected that the hip fracture risk would increase fourfold between ages 55 and 85.

Thus, older women are a key group that needs screen- ing for osteoporosis.

In addition, women experiencing menopause at or before age forty year old, either spontaneously or induced (eg, through bilateral oophorectomy, chemo- therapy, or pelvic radiation therapy), are at greater risk of low BMD than other women of the same age who have not reached menopause

.

2. Nutrition and exercise factors

A balanced diet, adequate calories, and appropriate nutrients are the foundation for development of all tissues, including bone. Supplementation with calcium and vitamin D may be necessary. Adequate and appro- priate nutrition is important for all persons. Several lifestyle factors are associated with the risk of low BMD and osteoporotic fracture. These include poor nutrition, insufficient physical activity, cigarette smo- king, and heavy alcohol consumption. Enormous data exist to recommend calcium intakes so important for bone health at various stages of life. Although the Institute of Medicine recommends calcium intakes of 800 mg/d for children aged 3 to 8 years and 1300 mg/d for children and adolescents aged 9 to 17 years, it is estimated that only about 25% of boys and 10% of girls aged 9 to 17 years meet these recommendations.

Factors contributing to low calcium intakes are restric-

tion of dairy products, a generally low consumption of

fruits and vegetables, and a high intake of low-calcium

beverages such as sodas. For older adults, calcium

intake should be maintained at 1000 to 1500 mg/d, yet

only about 50% to 60% of this population meets this

recommendation

. According to the China report

, usually urban residents have higher calcium intake from foods and calcium supplements, while rural residents have lower calcium intake.

Vitamin D is required for optimal calcium absorption and thus is also important for bone health. A recom- mended vitamin D intake of 400 to 600 IU/d has been established for adults. Regular physical activity has numerous health benefits for persons of all ages. Rural residents in China participated in more physical acti- vities and outdoor activities than those of urban resi- dents

.

GENETIC FACTORS AND BODY MASS INDEX

Genetic factors exert a strong and perhaps predo- minant influence on a woman’s peak bone mass, but physiological, environmental, and modifiable lifestyle factors can also play a significant role. In the Brown et al study, over 80% of the variability in peak BMD might be attributable to genetic factors

. First-degree relatives (eg, mother, sister) of women with osteoporo- sis also tend to have lower BMD than those with no family history of osteoporosis

. Moreover, a history of fracture in a first-degree relative also significantly increases the fracture risk. Kanis et al

. reported that a family history of fracture was found to be associated with significant increases in any osteoporotic fracture in a meta-analysis. Hip fracture risks were nearly 50～

127% higher if a hip fracture had occurred in a parent.

And risk ratios were slightly higher for hip fracture (RR, 1.63) than for any fracture (RR, 1.18) or for any osteoporotic fracture (RR, 1.22).

Body mass index (BMI) is one of the risk factors for postmenopausal osteoporotic fractures. One study shown that the US white woman’s BMI less than 21 kg/m

is a risk factor for low BMD

. Low weight or low BMI is a well-documented risk factor for future fracture, while high BMI may be protective. Especially,

excessive pursuit of thinness may preclude adequate nutrition and affect the health of bone resulting in osteoporosis. In the Kanis’s study

, the risk ratio is markedly higher at the BMI of 20 kg/m

or less. By contrast, between a BMI of 25 kg/m

and 35 kg/m

, the differences in risk ratio are smaller. There appears to be an inflection point at which increased BMI more than 22 kg/m

is associated with decreases in fracture risk. BMI might be helpful for evaluating the risk of osteoporotic fractures without BMD values.

ASSESSMENT OF

POSTMENOPAUSAL OSTEOPOROSIS

All postmenopausal women should be assessed for risk factors associated with osteoporosis and fracture.

Firstly a history (personal history of fracture after age 40, history of hip fracture in a parent, cigarette smoking, excess alcohol consumption, glucocorticoid use, or other secondary causes of osteoporosis, etc) taking and physical examination are essential in evaluating fracture risks and should include assessment for loss of height and change in posture. Secondly laboratory evaluation for secondary causes of osteo- porosis should be ruled out when osteoporosis is diagnosed. And predict fracture risk factors are based on assessment of BMD. Finally appropriate manage- ment should be considered.

Generally osteoporosis has no warning signs, and the first indication of the disease is a fracture. Osteoporotic fractures, particularly vertebral fractures, can be asso- ciated with chronic disabling pain. Roughly one third of vertebral fractures are painful, and two thirds are painless

. Marked height loss over the years may be a sign of underlying vertebral compression fractures, even without significant associated back pain. Height should be measured annually with an accurate method.

Besides, weight should also be recorded to identify

those women with low BMI and to be aware of weight

changes. A woman, after menopause, has risk for falls

which should be assessed. The risk of falls is also increased by use of medications that affect balance and coordination (eg, narcotic analgesics, antihypertensives) or by use of multiple medications. Additionally, obsta- cles and poor lighting in the home and work environ- ment also contribute to the risk of falls. These hazards can be assessed by questioning the postmenopausal women.

BMD measurement is still the most commonly used for diagnosing osteoporosis

, and it accounts for app- roximately 70 % of bone strength. The World Health Organization (WHO) defines osteoporosis in postmeno- pausal women over age 50 as BMD T-score less than or equal to 2.5 SDs below the mean at the total hip, femoral neck, or lumbar spine

. In 2010 the North American Menopause Society recommends that BMD be measured in the following populations: (1) All women age 65 and over, regardless of clinical risk factors; (2) Postmenopausal women with medical causes of bone loss (eg, steroid use, hyperparathy- roidism), regardless of age; (3) Postmenopausal women age 50 and over with additional risk factors (Fracture after menopause, BMI <21 kg/m

, History of hip fracture in a parent, Current smoker, Rheumatoid arthritis, Alcohol intake of more than two units per day); (4) Postmenopausal women with a fragility fracture (eg, fracture from a fall from standing height).

The spine may be a useful site for BMD measurement in early postmenopausal women because decreases in BMD can be faster at the spine than at the hip site. In addition, for women receiving osteoporosis therapy, BMD monitoring may not provide clinically useful information until after one to two years of treatment.

Stable BMD indicates successful therapy, whereas marked declines in BMD predict greater fracture risk

. Concerning the bone turnover markers, biochemical markers of bone turnover can be measured in serum or urine, including osteoclastic bone resorption markers (N-telopeptides, C-telopeptides, deoxypyridinoline) and osteoblast functioning markers (bone-specific alkaline

phosphatase, procollagen type I N-terminal propeptide, osteocalcin). Bone turnover markers cannot diagnose osteoporosis and have varying ability to predict fracture risk

. However, these tests may show an individual patient’s response to therapy earlier than BMD changes, sometimes within two to three months as opposed to the one to three years required with BMD. Most bone turnover markers vary greatly and are affected by food intake, so clinical utility has limitation.

MANAGEMENT OF

POSTMENOPAUSAL OSTEOPOROSIS

1. Nutrition

In the prevention and management of postmenopau-

sal osteoporosis, calcium and vitamin D, vitamin K,

protein should be focused on. Calcium, a mineral, can

generally be viewed as a weak antiresorptive agent as

well as an essential nutrient. Evidence has established

the role of adequate calcium intake in bone health,

primarily in the development of peak bone mass and in

preventing bone loss. Vitamin D is actually a steroid

prohormone rather than a vitamin, as it can be pro-

duced in the human body through the interaction of

sunlight with the skin. Nevertheless, this nutrient is

commonly characterized as a vitamin. It is essential for

the physiologic regulation and stimulation of intestinal

absorption of calcium

. Vitamin D deficiency will con-

tribute to declining calcium absorption. The Women’s

Health Initiative trial’s results shown that hip fractures

were significantly reduced in older women who were

adherent to the calcium and vitamin D regimen

.

According to another report, there is a high pre-

valence of calcium, protein and vitamin D insufficiency

in the menopausal women and elder people. Vitamin D

supplements can reduce the risk of falling provided the

daily dose of vitamin D is greater than 700 IU

.

Whereas a gradual decline in caloric intake with age

can be considered as an appropriate adjustment to the

progressive reduction in energy expenditure, the parallel

reduction in protein intake may be detrimental for maintaining the integrity and function of skeletal muscle and bone. Calcium and vitamin D supplements decrease the risk of proximal femur fracture. Optimal treatment of osteoporosis with any drug therapy also requires calcium and vitamin D intake meeting recom- mended levels. The preferred source of calcium is dietary. Calcium supplements need to be absorbable.

Dietary sources of vitamin D are limited to fortified dairy products and fatty fish. Therefore, the use of a supplement containing vitamin D is the most practical means of addressing vitamin D sufficiency.

Sufficient protein intakes are necessary to maintain the function of the musculoskeletal system, but they also decrease the complications that occur after an osteoporotic fracture. Correction of poor protein nutri- tion in patients with a recent hip fracture has been shown to improve the subsequent clinical course by significantly lowering the rate of complications

. The current predominant form of vitamin K is vitamin K1, found in green leafy vegetables. Approximately 34% of vitamin K is obtained from fats and oils in diet. The average dietary intake of vitamin K is approximately 340 µg/day. In one study, supplementation with vitamin K1 (1 mg/d) in conjunction with calcium, magnesium, zinc, and vitamin D appeared to be associated with beneficial effects on bone turnover and bone density at the femoral neck

. Another study suggested no benefit to 5 mg/day of vitamin K1 in preventing bone loss at the lumbar spine and proximal femur for postmeno- pausal women with adequate vitamin D intake who have osteopenia

. So the evidence that vitamin K1 is useful in the prevention or treatment of postmenopausal osteoporosis is lacking.

Generally, intakes of at least 1,000～1500 mg/day of calcium, 800 IU of vitamin D and of 1 g/kg body weight of protein can be recommended in the postmenopausal osteoporosis patients

.

EXERCISE AND FALLS

Immobilization is a very important cause of bone loss. Weight-bearing and strength-training exercises are beneficial to bone development and maintenance.

However, extreme exercise is not necessary to affect a bone benefit. Even mild forms of exercise that improve agility and balance can benefit the skeleton. The amount of weight-bearing exercise that is optimal for skeletal health in patients with osteoporosis is not known, but exercise forms an integral component of management

. In early postmenopausal women, strength-training provides small but significant benefits to bone mass

. A meta-analysis suggested that post- menopausal women who exercised increased their spinal BMD by approximately 2%

. Generally, active weight-bearing or strength-training exercises can in- crease bone mass if they increase muscle mass and strength.

Falls are one of the risk factors of osteoporosis and osteoporotic fractures, which are the precipitating factor in nearly 90% of all appendicular fractures

. Older women have a significantly higher risk for falls than do men of the same age. Exercise increasing strength may prevent falls by improving confidence and coordination, which can maintain bone mass by stimulating bone formation and by decreasing bone resorption. In addition, improving the home environment, for exam- ple, slippery floors, obstacles, insufficient lighting, is important measures aimed at preventing falls. Some randomized trials have shown that wearing hip protectors can markedly reduce hip fracture risk, particularly in the elderly living in nursing homes

. Thus, fall prevention should be an aspect of routine intervention for all postmenopausal women.

MAJOR PHARMACOLOGICAL MANAGEMENTS

Bisphosphonates are potent antiresorptive agents that

bind to hydroxyapatite crystals on the surface of bones, enter osteoclasts, and decrease resorptive actions by reducing the production of hydrogen ions. In addition, they have indirect effects. Bisphosphonates are useful for prevention and treatment of osteoporosis. They increase BMD at the spine, wrist, and hip, and decrease the risk of vertebral fractures by 30～50%

. The potency of bisphosphonates in inhibiting bone resorp- tion varies greatly from different compounds in vitro, so that the doses used clinically also vary. Alendronate and risedronate are common bisphosphonates used for osteoporosis in China, and they are available in oral formulations for daily and intermittent dosing regimens.

The overall safety profile of bisphosphonates is favo- rable. Most common adverse effect of oral bisphos- phonates is mild gastrointestinal disturbances, and some can rarely cause esophagitis.

Hormone therapy (HT) is an established approach for osteoporosis treatment and prevention, which can reduce the accelerated bone turnover induced by the menopause, and prevent bone loss at all skeletal sites regardless of age and duration of therapy. Results from observational studies and randomized placebo-controlled trials have shown that HT decreases the risk of vertebral and non-vertebral fractures (including hip fracture) by about 30%

. Clinical studies have demon- strated that HT can significantly reduce the incidence of fractures in elder women, and they may regain the lost bone during the treatment. The WHI, a 5-year RCT in postmenopausal women ages 50 to 79, reported that standard doses of HT significantly increased spine and total hip BMD by 4.5% and 3.7%, respectively

. However, HT has undesirable side effects. In particular, it may increase the risk of breast cancer, deep vein thrombosis and stroke. Uterine bleeding and breast pain commonly occur in women during HT. Therefore, alternatives to HT are being used increasingly in the prevention and treatment of postmenopausal osteo- porosis, for example, phytoestrogens. The phytoestro- gens could play an important role in the amelioration

of postmenopausal bone loss

. In particular, they might be more marked among menopausal Chinese patients with lower calcium intake and body weight

.

Selective estrogen receptor modulators (SERMs) are a class of compounds that can act as estrogen receptor (ER) agonists in some tissues while acting as ER antagonists in the others, depending on the target tissues. The first SERM tamoxifen has been used to treat breast cancer for more than 40 years. Now the family of SERMs becomes bigger and bigger. In terms of chemical constitution, the families of SERMs can be divided into three groups including thriphenylethy (synthesis estrogen) ― such as clomifene, tamoxifen and derivation of tamoxifen, benzothiophene ― such as raloxifene and its’ analogs, and benzopyrangl ― such as EM-652 and its’ analogs. Currently, raloxifene is the only SERM approved for the prevention and treatment of postmenopausal osteoporosis. It exhibits estrogen agonist properties in the bone. In the MORE trial, raloxifene prevents bone loss and reduces the risk of vertebral fractures by 30～50% in postmenopausal women with low bone mass, and with osteoporosis with or without prior vertebral fractures as shown

. So, the SERM raloxifene is most often considered for postmenopausal women with low bone mass or younger postmenopausal women with osteoporosis.

Calcitonin is a polypeptide hormone that inhibits osteoclast activity and therefore inhibits bone resorp- tion. It demonstrates positive effects on BMD at the lumbar spine in postmenopausal osteoporosis. In one study of 1,255 postmenopausal women with established osteoporosis, intranasal-spray calcitonin for 5 years significantly reduced the risk of new vertebral fracture by 33% compared with placebo

. In addition, calci- tonin may have an analgesic effect in women with acute vertebral fracture, and have shown to reduce bone pain from osteoporotic vertebral compression fractures.

Because calcitonin is a less effective agent than other

therapies (bisphosphonates) for osteoporosis, it is re-

served as an alternative for women who cannot or

choose not to take one of the other osteoporosis agents.

The most frequent side effects include nausea, local inflammation, and flushing of the face or hands when calcitonin is given as an injection, and local nasal irritation with the nasal spray formulation.

According to Chinese medical theory, the kidneys rule the bones and engender the marrow

. The low back is the mansion of the kidneys. Therefore, the growth and development of the bones as well as their strength is closely connected with the exuberance or decline of kidney essence. If the kidney essence is full and sufficient, the source of engenderment and transfor- mation of the bones and marrow have a source. The bones and marrow obtain nourishment and thus are fortified, strong, and forceful. The opposite of this easily leads to osteoporosis. In women, “at seven times seven (49 years of ages), the channels and vessels are vacuous, the kidney yin is exhausted.” Thus the postmenopausal osteoporosis is due to the vacuity and decline of kidney essence. Numerous clinical trials have been carried out over the last 20 years on the effects of Chinese medicine on postmenopausal osteoporosis

. These studies show that Chinese herbal medicine can increase bone density in post-menopausal women.

Therefore, to promote bone growth and density, women should mainly prescribe Chinese medicines which supplement the kidneys and strengthen the bones. The leading medicinal in the Chinese medicines formula are Ba Ji Tian，Xian Ling Pi，Zi He Che, Huang Qi, Long Gu, Mu Li and etc, which act as essential nutrients for providing the building blocks of the bones and for the treatment and prevention of osteoporosis.

In sum, all postmenopausal women should receive calcium supplementation to achieve total calcium of 1,200 mg/day for adults age 50 and older, and vitamin D supplements of 800 IU/day are also recommended.

Postmenopausal should be encouraged to exercise re- gularly to improve grace and agility, which will decrease their risk of falls. In addition, diet should be modified to decrease consumption of salt, animal

protein, excessive alcohol consumption, all of which may increase the risk of osteoporotic fractures. Finally, appropriate osteoporosis drug therapy, including Chinese medicines, should be recommended.

Considering the aging population, longer life expectancy, and many dramatic changes in people’s lifestyles during recent years in China, although the prevalence of postmenopausal osteoporosis in China remains lower than that of other industrialized coun- tries

, future studies are needed and more effort should be made to increase Chinese people’s awareness re- garding osteoporosis and to promote good bone health.

REFERENCES

1. Consensus development conference: diagnosis, pro- phylaxis, and treatment of osteoporosis. Am J Med 1993;94:646-50.

2. NIH Consensus Development Panel on Osteoporo- sis Prevention, Diagnosis, and Therapy: Osteoporo- sis prevention, diagnosis and therapy. JAMA 2001;

285:785-95．

3. Kanis JA. Assessment of fracture risk and its application to screening for postmenopausal osteo- porosis: synopsis of a WHO report. WHO Study Group. Osteoporos Int 1994;4:368-81.

4. Melton LJ 3rd, Thamer M, Ray NF, Chan JK, Chesnut CH 3rd, Einhorn TA, et al. Fractures attributable to osteoporosis: report from the Natio- nal Osteoporosis Foundation. J Bone Miner Res 1997;12:16-23.

5. U.S. Dept. of Health and Human Services. Bone health and osteoporosis: A report of the Surgeon General Public Health Service, Office of the Surgeon General; Washington, D.C. http://www.

surgeongeneral.gov/library/bonehealth/content.html (assessed June 30, 2008).

6. National Osteoporosis Foundation. http://www.nof.

org/osteoporosis/diseasefacts.htm (assessed December

30, 2006).

7. Wang Y, Tao Y, Hyman ME, Li J, Chen Y. Osteo- porosis in China. Osteoporos Int 2009;20:1651-62.

8. Recker R, Lappe J, Davies K, Heaney R. Cha- racterization of perimenopausal bone loss: a pro- spective study. J Bone Miner Res 2000;15:1965-73.

9. Pouilles JM, Tremollieres F, Ribot C. Vertebral bone loss in perimenopause: results of a 7-year longitudinal study. Presse Med 1996;25:277-80.

10. Devine A, Dick IM, Dhaliwal SS, Naheed R, Beilby J, Prince RL. Prediction of incident osteo- porotic fractures in elderly women using the free estradiol index. Osteoporos Int 2005;16:216-21.

11. Francucci CM, Romagni P, Camilletti A, Fiscaletti P, Amoroso L, Cenci G, et al. Effect of natural early menopause on bone mineral density. Maturitas 2008;59:323-8.

12. Gu W, Rennie KL, Lin X, Wang Y, Yu Z. Diffe- rences in bone mineral status between urban and rural Chinese men and women. Bone 2007;41:393-9.

13. Brown LB, Streeten EA, Shapiro JR, McBride D, Shuldiner AR, Peyser PA, et al. Genetic and envi- ronmental influences on bone mineral density in pre- and post-menopausal women. Osteoporos Int 2005;16:1849-56.

14. Evans RA, Marel GM, Lancaster EK. Bone mass is low in relatives of osteoporotic patients. Ann Intern Med 1988;109:870-3.

15. Kanis JA, Johnell O, De Laet C, Johansson H, Oden A, Delmas P, et al. A meta-analysis of pre- vious fracture and subsequent fracture risk. Bone 2004;35:375-82.

16. Mandato VD, Sammartino A, Di Carlo C, Tommaselli GA, Tauchmanovà L, D'Elia A, et al. Evaluation of skeletal status by quantitative ultrasonometry in post- menopausal women without known risk factors for osteoporosis. Gynecol Endocrinol 2005;21:149-53.

17. Kanis JA, for the World Health Organization Scientific Group. Assessment of Osteoporosis at the Primary Health Care Level. Technical Report.

World Health Organization Collaborating Centre for

Metabolic Bone Diseases. Sheffield, UK: University of Sheffield, 2008:100-31.

18. Majumdar SR, Kim N, Colman I, Chahal AM, Raymond G, Jen H, et al. Incidental vertebral fractures discovered with chest radiography in the emergency department: prevalence, recognition, and osteoporosis management in a cohort of elderly patients. Arch Intern Med 2005;165:905-9.

19. Management of osteoporosis in postmenopausal women: 2010 position statement of The North American Menopause Society. Menopause 2010;17:

25-54.

20. Schousboe JT, Bauer DC, Nyman JA, Kane RL, Melton LJ, Ensrud KE. Potential for bone turnover markers to cost-effectively identify and select post-menopausal osteopenic women at high risk of fracture for bisphosphonate therapy. Osteoporos Int 2007;18:201-10.

21. Delmas PD, Munoz F, Black DM, Cosman F, Boonen S, Watts NB, et al. Effects of yearly zoledronic acid 5 mg on bone turnover markers and relation of PINP with fracture reduction in postmenopausal women with osteoporosis. J Bone Miner Res 2009;24:1544-51.

22. Heaney RP. Optimal vitamin D status. J Bone Miner Res 2009;24:755.

23. Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 2006;354:669-83.

24. Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC, Staehelin HB, Bazemore MG, Zee RY, et al.

Effect of Vitamin D on falls: a meta-analysis.

JAMA 2004;291:1999-2006.

25. Rizzoli R, Bonjour JP. Dietary protein and bone health. J Bone Miner Res 2004;19:527-31.

26. Braam LA, Knapen MH, Geusens P, Brouns F,

Hamulyák K, Gerichhausen MJ, et al. Vitamin K1

supplementation retards bone loss in postmeno-

pausal women between 50 and 60 years of age.

Calcif Tissue Int 2003;73:21-6.

27. Bolton-Smith C, McMurdo ME, Paterson CR.

Two-year randomized controlled trial of vitamin K1 (phylloquinone) and Vitamin D3 plus calcium on the bone health of older women. J Bone Miner Res 2007;22:509-19.

28. Tang BM, Eslick GD, Nowson C, Smith C, Bensoussan A. Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet 2007;370:

657-66.

29. Bonaiuti D, Shea B, Iovine R, Negrini S, Robinson V, Kemper HC, et al. Exercise for preventing and treating osteoporosis in postmenopausal women.

Cochrane Database Syst Rev 2002;(3):CD000333.

30. Snow-Harter C, Bouxsein ML, Lewis BT, Carter DR, Marcus R. Effects of resistance and endurance exercise on bone mineral status of young women: a randomized exercise intervention trial. J Bone Miner Res 1992;7:761-9.

31. Kelley GA, Kelley KS, Tran ZV. Exercise and lumbar spine bone mineral density in postmeno- pausal women: a meta-analysis of individual patient data. J Gerontol A Biol Sci Med Sci 2002;57:

599-604.

32. Komatsu T, Kim KJ, Kaminai T, Okuizumi H, Kamioka H, Okada S, et al. Clinical factors as predictors of the risk of falls and subsequent bone fractures due to osteoporosis in postmenopausal women. J Bone Miner Metab 2006;24:419-24.

33. Kiel DP, Magaziner J, Zimmerman S, Ball L, Barton BA, Brown KM, et al. Efficacy of a hip protector to prevent hip fracture in nursing home residents: the HIP PRO randomized controlled trial.

JAMA 2007;298:413-22.

34. Reginster J, Minne HW, Sorensen OH, Hooper M, Roux C, Brandi ML, et al. Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporo-

sis. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group. Osteoporos Int 2000;11:83- 91.

35. Geusens P. Strategies for treatment to prevent fragility fractures in postmenopausal women. Best Pract Res Clin Rheumatol 2009;23:727-40.

36. Cauley JA, Robbins J, Chen Z, Cummings SR, Jackson RD, LaCroix AZ, et al. Effects of estrogen plus progestin on risk of fracture and bone mineral density: the Women's Health Initiative randomized trial. JAMA 2003;290:1729-38.

37. Lewiecki EM. Phytoestrogens and their role in the management of postmenopausal osteoporosis. South Med J 2009;102:111-2.

38. Chen YM, Ho SC, Lam SS, Ho SS, Woo JL.

Beneficial effect of soy isoflavones on bone mine- ral content was modified by years since meno- pause, body weight, and calcium intake: a double- blind, randomized, controlled trial. Menopause 2004;11:246-54.

39. Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK, et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA 1999;282:637-45.

40. Chesnut CH 3rd, Silverman S, Andriano K, Genant H, Gimona A, Harris S, et al. A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study. PROOF Study Group. Am J Med 2000;109:267-76.

41. Ruan YG, Ruanshi XS. Overview in the treatment of postmenopausal osteoporosis with TCM. Guiding Journal of TCM 2007;13:81-2.

42. Luo Q, Qiu MY, Fu XF. Chinese medicine for postmenopausal osteoporosis impact analysis. China Modern Medicine 2009;16:92-4.

43. Holt G, Khaw KT, Reid DM, Compston JE, Bhalla

A, Woolf AD, et al. Prevalence of osteoporotic bone mineral density at the hip in Britain differs substantially from the US over 50 years of age:

implications for clinical densitometry. Br J Radiol 2002;75:736-42.

Peer Reviewers' Commentary

The author introduced the current status of osteoporosis in China. The aging of the population and lifestyle changes make postmenopausal osteoporosis a major public health problem throughout the world, not only in developed countries, but also in developing countries, such as China. The author said that the prevalence of postmenopausal osteoporosis in China remains lower than that of other developed countries. The author pointed out that future studies are needed and more effort should be made to increase the awareness of Chinese regarding osteoporosis and to reduce osteoporotic complications. The same situation exists in Korea, and we should increase people's awareness regarding osteoporosis and implement health policies for reducing osteoporosis prevalence.

(Summary: Editorial Committee)