Protecting a Woman’s Skeleton

Osteoporosis Vol. 8 No. 3 December 2010 pp. 237-240 □ Review Article □

237

Protecting a Woman’s Skeleton

Min Hyung Jung, Heung Yeol Kim

Department of Obstetrics & Gynecology, School of Medicine, Kyung Hee Medical Center, Kyung Hee University, Seoul, Department of Obstetrics & Gynecology

, Kosin University, Busan, Korea

Osteoporosis, the most common bone disease, is a silent condition resulting in increased fracture risk.

Preventive methods for adulthood, early recognition of osteoporosis followed by timely and effective management can reduce fracture risk. Several pharmacologic therapies are currently available, and when choosing from the available options, clinicians should consider the efficacy and safety profiles of each therapy as well as the individual patient’s needs and overall health. Ideally, therapy should satisfy multiple criteria: fracture protection across multiple skeletal sites; rapid onset of action to maximize the timing of fracture protection; and minimal side effects with proven long-term safety.

Key Words: Osteoporosis, Prevention, Screening, Treatment

Received: March 15, 2010 Revised: March 29, 2010 Accepted: April 5, 2010

Corresponding Author: Heung Yeol Kim, Department of Obstetrics

& Gynecology, College of Medicine, Kosin University, 34 Amnam-dong, Seo-gu, Busan 602-702, Korea

Tel: +82-51-990-6226, Fax: +82-51-990-3300 E-mail: [email protected]

Over the course of the next two decades, dramatic increases in the incidence of osteoporosis are expected in the United States and other developed nations due to aging populations. Unless effective preventive measures are instituted, in just 15 years an estimated 1 in 2 Americans over the age of 50 years will have, or be at high risk of developing, osteoporosis of the hip.1 The risk of osteoporosis at any skeletal site will be even higher. The consequences of an epidemic of osteoporo- sis will be devastating on a number of levels including the individual, their families and caregivers, and society at large. Fractures, which are the most important consequence of osteoporosis, increase a patient's risk of disability and premature death. Fractures also impose a significant financial burden on both the individual and society. In the last 20 to 30 years, considerable pro- gress has been made in the scientific understanding of

bone health and the factors that lead to osteoporosis.

Based on this scientific knowledge, it now seems clear that osteoporosis can be prevented in the vast majority of individuals, particularly the large number of post- menopausal women who are afflicted with the disease.

In those individuals who ultimately develop osteoporo- sis, scientific advances have also resulted in effective methods for early diagnosis and numerous treatment options. Physicians and other health care providers should become familiar with advances in the pre- vention, diagnosis, and treatment of osteoporosis in order to support lifelong bone health in their patients.

PEAK BONE MASS

Peak bone mass is defined as the maximum bone mass attained during skeletal growth. It is reached in nearly all adults by 30 years of age. Although osteo- porosis most commonly occurs in older adults- particularly older women-its prevention should begin at a much younger age by encouraging a lifestyle that facilitates the attainment of maximal peak bone mass.

Once peak bone mass has been attained, women should

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be encouraged to adopt or maintain lifestyle practices that preserve as much peak bone mass as possible.

Substantial skeletal growth occurs in infancy, when rudimentary bone is rapidly replaced by more mature bone. After infancy and before puberty, children tend to experience a slower growth in bone mass.

By age 18 years, skeletal growth is nearly complete, with minor accumulations in bone density occurring until around the age of 30 years. In most women between the ages of 30 years and menopause, bone formation is approximately equal to bone resorption, therefore minimal change occurs in total bone mass.

At menopause, lower estrogen levels trigger an increase in both resorption and formation, however, during this time period resorption predominates and bone mass is lost. During the first few years after the onset of menopause, the rate of bone loss is rapid. Loss of bone mass persists throughout the postmenopausal years although the rate of bone loss slows in most women 4-7 years after the cessation of menses.

Many factors, including age, gender, race, genetics, reproductive status, calcium levels, and exercise, affect bone mass.

Cortical bone mass plotted by age, sex, and ethnicity.

On average, peak bone mass is one fourth to one third greater in men than in women.

Following the attainment of peak bone mass, bone loss occurs as a function of age in both males and females. However, women experience greater bone loss in the early post- menopausal years. This period of rapid bone loss ends 4 to 7 years after the onset of menopause and bone loss continues thereafter at a more gradual rate. Since women have a lower peak bone mass and experience a period of rapid bone loss at the time of menopause, they are likely to reach the “fracture threshold” (the BMD at which the risk of fracture significantly increases) earlier than men. Over a lifetime, women lose about 35% of cortical bone and 50% of trabecular bone, whereas men lose only about two-thirds of this amount.

The peak bone mass attained by any given individual is dependent on both biological and lifestyle factors.

About 85% of peak bone mass is determined by genetics.

Dietary choices play an important role in building and maintaining bone mass throughout life, primarily by providing bone-building nutrients and by influencing absorption and retention of these nutrients. Calcium and vitamin D, in particular, play crucial roles in bone health, although other nutrients are involved as well.

Adequate intake of protein and calories is also necessary for maximizing peak bone mass.

Physical activity plays an important role in deter- mining peak bone mass because the body constantly monitors the strain on bones caused by muscle action, and any substantial increase in these forces signals the need to build more bone. Thus, adequate physical activity helps to maximize peak bone mass. Excessive, intense exercise that results in amenorrhea, however, will compromise bone mass accretion in adolescent girls and young adult women. A number of hormones are also involved in the growth of the skeleton. These include the calcium-regulating hormones (parathyroid hormone, calcitriol, and calcitonin), gonadal steroid hormones (especially estrogen in females and test- osterone in males), growth hormone, and thyroid hormones. After individuals attain peak bone mass, lifelong bone health can be optimized by maintaining as much of this peak bone mass as possible.

BIOLOGICAL AND MOLECULAR MECHANISMS INVOLVED IN BONE LOSS IN POSTMENOPAUSAL WOMEN

Estrogen deficiency leads to accelerated bone

resorption and consequent increased risk of fracture

through various cytokines that influence osteoclast

formation and lifespan. After menopause, when

estrogen levels decline, tissue necrosis factor (TNF)

production by monocytes increases. In addition, cells of

Min Hyung Jung, Heung Yeol Kim：Protecting a Woman’s Skeleton

239 the stromal/osteoblastic lineage become more sensitive

to interleukin (IL)-1.

RANK ligand (RANkL) is a cytokine intimately involved in the formation and activation of osteoclasts and thus promotes bone resorption. Osteoprotegerin is a soluble receptor for RANKL and therefore serves as an endogenous antagonist of the actions of RANKL.

Estrogen deficiency tilts the balance in favor of RANKL and therefore promotes osteoclast activation.

PREVENTION OF BONE LOSS

Strategies to prevent bone loss-especially early post- menopausal bone loss-can minimize the physical, social, and economic consequences of osteoporosis.

The goals of prevention are to optimize skeletal development and maximize peak bone mass at skeletal maturity, prevent menopause-related, age-related, and secondary causes of bone loss, preserve the structural integrity of the skeleton, prevent fractures.

Because the presence of a fracture is a very strong predictor of a subsequent fracture, all women who experience an osteoporosis-related fracture should begin therapy for osteoporosis. All therapies that are FDA approved for the treatment of osteoporosis have anti-fracture efficacy documented by clinical trials.

An adequate calcium intake is necessary for bone health at all ages. Given that calcium intake from foods is inadequate in an overwhelming majority of women in the US,

the use of calcium supplements is a common and appropriate recommendation. However, health care providers must be certain that patients are aware that calcium supplementation does not prevent the accelerated bone loss that occurs in the early postmenopausal years.

Meta-analysis was conducted to estimate the effec- tiveness of vitamin D supplementation in preventing hip and nonvertebral fractures in older persons.

Oral vitamin D supplementation was effective in reducing hip fractures only at doses between 700 and

800 IU/day. The size of the symbols is proportional to the number of patients in each trial. Lower doses were not effective. Similar results were seen for nonvertebral fractures.

FDA approved therapies for the prevention of bone loss are estrogen, the bisphosphonates alendronate and risedronate, and the selective estrogen-receptor modula- tor raloxifene.

SUMMARY AND CONCLUSIONS

Women and their healthcare providers must pay close attention to factors that influence bone health in childhood as well as adulthood. Since up to 20% of lifetime bone loss can occur in the first 5 to 7 years following menopause, the initiation of HT for symptom relief is also an effective method for preventing osteoporosis and osteoporosis-related fracture. More- over, it is considerably less expensive than other currently available antiresorptive therapies. Women treated with HT to relieve menopausal symptoms do not need another antiresorptive agent. The use of postmenopausal HT is a personal, individualized deci- sion. Patients and physicians should take into account a woman's preferences and individual benefits and risks when considering the use of HT. When prescribing HT solely for the prevention of postmenopausal osteo- porosis, therapy should only be considered for women at significant risk of osteoporosis, and non-estrogen medications should be carefully considered.

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Peer Reviewers' Commentary

The main consequence of osteoporosis is an increased incidence of fractures, which increase as a woman ages. These result not only in patient’s risk of disability but also in premature death. Since up to 20%

of lifetime bone loss of women can occur in the first 5 to 7 years following menopause, the initiation of HT for symptom relief is also an effective method for preventing osteoporosis and osteoporosis-related fracture. The author described predicting fracture risk and several pharmacologic therapies for fracture prevention. A number of options are available for the prevention and treatment of osteoporosis. When choosing from the available options, clinicians should consider the efficacy and safety profiles of each therapy as well as the individual patient’s need and overall health. It is well designed article regarding protecting strategies for woman’s skeleton and should be helpful in reducing rates of fracture.

(Summary: Editorial Committee)