Bone Health: Osteoporosis Prevention Strategies
WHEC Practice Bulletin and Clinical Management Guidelines for healthcare providers. Educational grant provided by Women's Health and Education Center (WHEC).
Osteoporosis is an important health problem affecting mature women. Americans with osteoporosis or with low bone mass, approximately 80% are women. Osteoporosis-related fractures will occur in more than 40% of women over the age of 50. Hip fractures will occur in more than 40% of women over the age of 50. An estimated 1.3 to 1.5 million fractures occurring annually are attributed to osteoporosis, accounts for about 15% of the total. Within 1 year after a hip fracture, up to 20% of the victims will die, 25% of the survivors will be confined to long-term care facilities, and 50% will experience long-term loss of mobility. Spinal fractures can be associated with pain, loss of height, and deformities. Osteoporosis also is associated with tooth loss and the resorption of alveolar ridge.
Obstetricians and gynecologists play a major role in the prevention, diagnosis, and treatment of osteoporosis as outlined in this document. It is intended as an educational tool that presents current information.
The World Health Organization (WHO) defines low bone density, or osteopenia as a bone mineral density between 1 and 2.5 standard deviations below the young adult mean and the osteoporosis be defined as a bone mineral density 2.5 standard deviations or more below the young adult peak mean. At the spine and hip, a 1 standard deviation decrease in bone mass is associated with approximately a twofold increase in fracture risk.
Key Bone Density Definitions (1):
Osteoporosis: A disease of the bone that is characterized by a predisposition to low-trauma fractures caused by low bone mass and disordered bone architecture. Defined by the WHO as a bone density T-score at or below -2.5 of normal peak bone density values for sex-matched young adults. A diagnosis of osteoporosis can also be made by proving the presence of a low-impact vertebral, hip, or wrist fracture.
Low bone mass (previously osteopenia): Defined as a bone density T-score between -1 and -2.5 below the young adult mean.
T-score: The difference in standard deviations between the value for the patient being tested and the mean value of a sex-matched group of adults aged 25 to 45 years. A T-score of 0 indicates that the person being tested has a BMD that is at the mean for adults aged 25 to 45 years. Four standard deviations approximate the range of measurements from the 5th to 95th percentile.
Z-score: The difference in standard deviations between the mean BMD of the patient being tested and a group of people of the same age and sex. A low Z-score may warrant an investigation for a secondary cause of osteoporosis, such as hypercalcemia, low 25-hydroxy vitamin D, or malabsorption syndrome.
BMD: bone mineral density; WHO: World Health Organization.
The functional part of bone is the remodeling unit. Bone can be divided into two major types: cortical and trabecular. Cortical bone forms the outer shell of all bones and accounts for 75% of total bone mass. Trabecular bone is the spongy, interlacing network of struts that forms the internal support within the cortical bone. Trabecular bone is concentrated in the vertebral bodies and pelvis and at the ends of the long bones. It accounts for 25% of total bone mass, but counts for most of the surface area of the bone. Bone remodeling units are limited to the bone surface. Because trabecular bone has large surface area, it has a higher turnover rate than cortical bone (1).
The remodeling cycle can be conveniently divided into four phases: resting, resorption, reversal and formation. Each remodeling cycle may take several months to complete. During resting phase, stem cells from the bonemarrow are attracted to the bone surface and differentiate into osteoclasts. During the resorption phase, the osteoclasts remove bone using an acid pH to dissolve the minerals and proteolytic enzymes to digest the bone proteins. During reversal phase, the osteoclasts cease removing the bone and mesenchymal stem cells are attracted to the bone surface and differentiate into osteoblasts. During the formation phase, osteoblasts make new bone by first laying down a protein matrix (osteoid), which is then mineralized. Bone formation and resorption is an ongoing process that usually is balanced in young adults who have adequate nutrition and exercise and normal puberty.
Bone mass peaks at approximately 30 years in both men and women. After reaching peak bone mass, about 0.4% of bone is lost per year in both sexes. In addition to this loss, women also lose approximately 2% of cortical and 5% of trabecular bone per year for the first 5 to 8 years following menopause (2). With aging, the coordinated balance between osteoclasts and osteoblasts may be disturbed, resulting in excessive bone loss. In women who are recently menopausal, excess bone loss is commonly due to excessive osteoblasts resorption. In later postmenopausal years, suppressed osteoblasts activity and inadequate formation of bone may play a major role in the progression of osteoporosis.
Factors Affecting Bone Mass:
Bone mass is affected by these factors: family history, hormone levels, lifestyle and habits, nutrition, medications, and diseases that affect bone metabolism. Many studies have shown that the risk of osteoporosis is greater for white and Asian women than for African American women. Mexican American women have an intermediate risk. These racial differences are probably due, in part, to genetic determinants of body size, body composition, and bone metabolism. Genetic factors play a role in determining bone mass.
Estradiol, testosterone, progesterone, cortisol, parathyroid hormone, thyroxine, growth hormone, and insulin all can influence bone mass. The mechanism by which estradiol regulates bone mass are not completely defined. Many lifestyle factors and habits influence bone mass. Cigarette smoking, excessive use of alcohol and high caffeine intake may be associated with decreased bone mass and an increased risk of hip fracture. Dietary calcium intake is an important modular of bone mass, especially during childhood, adolescence, and advanced age. Childhood calcium intake appears to influence adult hipbone mass (3).
Vitamin D and its metabolites are essential to calcium metabolism and maintenance of mineral balance. In the United States, vitamin D deficiency rarely occurs except in select populations, such as those who are institutionalized with inadequate dietary intake and insufficient exposure to the sun. High protein diets acutely increase calcium excretion, but long-term, high protein diets are not associated with excess bone loss. Diets high in phosphorus can result in excess calcium loss, but daily phosphorus intake less than 2,00 mg is not harmful to bone (recommended daily allowance in menopausal women is 700 mg ).
Systemic medications such as glucocorticoids, thyroxine, and heparin can cause decreased bone mass. They have a direct effect on bone, causing inhibition of bone formation and enhancing bone resorption, and also decrease calcium absorption from the intestine and increase renal excretion of calcium. Hyperthyroidism is associated with decreased bone mass. Many metabolic bone diseases are associated with bone loss. These diseases often can be differentiated based on the measurement of serum calcium, phosphorus, and alkaline phosphatase. Osteoporosis can be caused by systemic diseases of the endocrine, hematopoietic, gastrointestinal and connective tissue systems. When osteoporosis is caused by systemic diseases, it is called secondary osteoporosis.
Summary of Clinical Laboratory Data in Common Metabolic Diseases of the Bone:
Source: ACOG Educational Bulletin, # 246, April 1998
Renal Failure; renal elevated osteodystrophy
Normal; (sometimes elevated)
Diagnosis needs to take into account other risk factors, including age, sex, white race, smoking and a family history of osteoporosis. There is no current accurate measurement of overall bone strength. Imaging technology is now available to determine bone mass with minimal radiation exposure, high accuracy, and high precision. Dual X-ray absorptiometry (DXA) is preferred by most authorities. The precision of the measurement is approximately 1%. The radiation dose is less than 5 mrem. All modern DXA devices have an examination time in the range of 5 minutes. Dual X-ray absorptiometry instruments are available, which measure bone mass at peripheral sites such as in the forearm. Measurement of forearm, wrist, or hand bone density may not predict hip fractures as accurately as the direct measurement of hip-bone mass. One disadvantage of DXA is that bone spurs, aortic calcium, and arthritis may falsely elevate the reported bone density. Ultrasound bone mass measurement is a new technique that offers the potential advantage of avoiding exposure to ionizing radiation.
Bone mass tests typically report three values: (i) an absolute value for the bone mass expressed as grams per square centimeter, (ii) a value for bone mass relative to a sex and age-matched reference population, usually called Z-score, and (iii) a value for bone mass relative to the mean peak bone mass, usually called a T-score or a young adult Z-score.
In addition to bone density instruments, bone mass can be estimated through serial height measurements. Measurement of current height and comparison to reported maximal adult height can help establish the presumptive diagnosis of osteoporosis. Osteoporosis is likely to be present if the patient has lost more than 1 inch in height from her maximal adult height and the clinical setting is consistent with a diagnosis of osteoporosis.
Biochemical markers can be useful to help identify women with high bone turnover and to monitor the effects of osteoporosis treatment. Markers that measure the rate of bone formation include serum bone alkaline phosphatase, serum osteocalcin, and serum procollagen I extension peptides. Markers that show the rate of bone resorption include urinary N-telopeptide, collagen crosslinks, urinary deoxypyridinoline, and urinary hydroxyproline (5).
A healthy life-style is important for those at risk for osteoporosis. Cessation of smoking eliminates the effects of nicotine on estrogen binding. Moderation in alcohol and caffeine intake will improve general health, and weight-bearing exercises provide mechanical stimulation for bone remodeling. Sedentary life-style is associated with reduced bone mass. The benefits of physical exercise include maintenance of bone mass and an increase in muscle strength and coordination. The risk of falling increases substantially with aging. Most falls that result in hip fractures occur indoors. The living environment should be monitored to reduce the risk of falling.
Prevention of osteoporosis begins in childhood and adequate calcium intake is important. Many children and adolescents do not achieve the recommended daily intake of calcium. Insufficient calcium intake also can accelerate age-associated bone loss.
Optimal Calcium Requirements [NIH Consensus Statement 1994; 12(4):7]
Age or Clinical State
Recommended Elemental Calcium Intake (mg)
Children (Age 1-5 years)
Children (Age 6-10 Years)
Adult women (premenopausal)
Adult women (menopausal or Hypoestrogenic on Estrogen Replacement Therapy)
Adult women (menopausal or Hypoestrogenic not on Estrogen Replacement Therapy)
In women with associated osteoporosis, calcium, vitamin D supplementation, and an exercise program should be considered. Most pharmacologic options for the prevention and treatment of postmenopausal osteoporosis reduce bone resorption and remodeling, but not all agents are equally effective in increasing both bone mineral density (BMD) and bone turnover vary between skeletal sites.
- Calcium: its mechanism of action by increased availability. Its deficiency causes bone loss. Reduction in fracture is by use of calcium with vitamin D. It is recommended for adolescents, lactating women, and osteoporosis risk factors including age. The recommended doses for calcium intake are listed above. It should not exceed 2,000 mg/day to prevent the risk of hypercalcuria, hypercalcemia. Calcium supplementation may provide a convenient means for reaching the daily dietary calcium goal without adding significant calories to the diet. Calcium citrate is more soluble and better absorbed than calcium carbonate in both fasting normal and achlorhydric individual.
- Vitamin D: it increases intestinal absorption of calcium. Its direct effect is unknown; it increases mass when combined with calcium and reduces fracture risk. Overdose in elderly can lead to renal failure, and hypercalcuria and hypercalcemia with increased dose is seen.
- Estrogen: it reduces bone resorption by inhibiting osteoclasts. It slows bone loss; increases mass slightly, and affects all types of bone. It is recommended as first-line choice for prevention in absence of contraindication in menopausal women. Estrogen replacement initiated during perimenopausal or soon after the menopause prevents the early phase of menopausal bone loss and decreases the subsequent risk of fracture by approximately 50%. For menopausal women taking estrogen replacement therapy, the addition of a progestin does not significantly increase bone mass; the optimum duration of this therapy is not well established. Risks of uterine bleeding, endometrial hyperplasia, endometrial carcinoma, breast cancer, and stroke are higher in patients taking estrogen replacement therapy.
- Alendronate (Fosamax) and Risedronate (Actonel): they are bisphosphonate that reduces bone resorption by inhibiting osteoclasts; slows bone loss and increases bone mass. Bisphosphonate are analogues of inorganic pyrophosphate, and a number of these are currently under development. Vertebral fractures are reduced by 48% in the women treated with alendronate and risedronate. They are poorly absorbed from gastrointestinal tract and are recommended to be taken in the morning with 8 ounces of water, prior to any food or beverage. No food or beverage should be taken for the next 30 minutes to allow the alendronate to be absorbed. After taking alendronate or risedronate the woman should remain in an upright position, either sitting or standing to minimize the possibility of abdominal discomfort. The major side effects are abdominal discomfort, upper gastrointestinal bleeding, and musculoskeletal pain. One potential advantage of alendronate and risedronate are that they remain tightly bound to the surface of the bone for many years. It is not recommended for the patients with the renal failure or upper gastrointestinal problems. FDA has approved their use for the prevention of osteoporosis.
- Calcitonin: it is a synthetic polypeptide based on salmon Calcitonin, is available in injectable form and as nasal spray. It inhibits bone resorption and is approved for the treatment of osteoporosis in women who are postmenopausal for at least 5 years. It increases vertebral bone mass and significantly reduces new vertebral fractures. Objection to injectables now can be avoided by intranasal spray. Risks are: development of neutralizing antibodies-effect and absorption is variable. One spray in one nostril delivers the recommended dose of 200 IU of salmon calcitonin.
- Selective Estrogen Receptor Modulators (SERMs) - (Raloxifene): it works as weak estrogen agonists in some systems, and estrogen antagonists in others. Raloxifene decreases the number and activity of osteoclasts and is approved for the prevention and treatment of postmenopausal osteoporosis. It decreases the incidence of vertebral fractures by 30% to 50% and increases bone mineral density (BMD) in the spine and femoral neck. Raloxifene is associated with a reduced risk of estrogen-dependent breast cancer, and may lower the risk of heart disease and stroke in women at high risk. However, the long-term effects of raloxifene on the vascular system are unknown, and increased risk of thromboembolic events similar to that reported with estrogens has been observed.
As a result of its tendency to cause or exacerbate hot flashes, raloxifene is not recommended for newly menopausal women or for the treatment of vasomotor symptoms. However, it can reduce the risk of breast cancer in postmenopausal women at low risk of the disease, and is currently being evaluated for use in reducing the incidence of breast cancer in women at increased risk (6).
- Parathyroid Hormone (PTH): it controls the distribution of calcium and phosphate in the body, stimulating bone formation and resorption and either increasing or decreasing bone mass, depending on the mode of administration. Parathyroid hormone (PTH) has recently been approved by the FDA for the treatment of osteoporosis in postmenopausal women at high risk of fracture. PTH (teriparatide) 40 micro gm. reduces the incidence of vertebral and non-vertebral fractures.
- Combination Treatments: hormone therapy and bisphosphonate combination have been studied recently in several clinical trial. Significantly greater increases in BMD were reported with combination treatment than either therapy alone, with no observed increase in side effects. The co-administration of PTH with either bisphosphonates or SERMS is an exciting prospect, though clinical trial data to support the use is currently lacking.
- Fluoride: it is a mineral that stimulates osteoblasts to produce new bone. When fluoride is administered at doses of 75 mg daily or more, the new bone formed is dense but may be structurally weak and susceptible to fracture. Lower doses of fluoride, administered in a slow-release formulation for 28 months, have been demonstrated to both improve bone density and simultaneously decrease fracture risk. The most common side effects of treatment with fluoride are gastric irritation and lower extremity pain. Currently, there is insufficient evidence to support the safety and efficacy of sodium fluoride therapy for the treatment of osteoporosis.
- Progestins and Androgens: they reduce bone resorption by inhibiting osteoblasts and slow the bone loss. In women on estrogen replacement therapy unless hysterectomized; are not recommended as sole agents. Risks are that doses required to positively affect bone; causes reduction in high-density lipoprotein and elevation of low-density lipoprotein.
When should treatment for osteoporosis begin and how should patient be followed:
Lower bone density T-scores generally indicate more severe osteoporosis and higher risk of fracture. Every decrease of 1 standard deviation from age-adjusted bone density represents approximately a 10-12% change in bone mineral density (BMD) and an increase in the risk of fracture by a factor of approximately 2. Although few would withhold treatment from a woman with osteoporosis (T-score less than -2.5), whether to treat a woman with higher bone density scores has become a subject for debate. The National Osteoporosis Foundation (NOF) has chosen a T-score of -2 for women without risk factors and -1.5 for women with additional risk factors as the threshold for therapeutic treatment (7). The Z-score may help in determining an alternative strategy, particularly with the Z-score is less than -1 and the patient would not have qualified for therapy solely on the criteria discussed above. Under these circumstances, a secondary cause for the bone loss should be sought. Monitoring a patient's response to treatment requires central bone densitometry. For women receiving osteoporosis therapy, bone mineral density (BMD) monitoring before 2 years of therapy are completed does not provide clinically useful information and may lead to erroneous assumption about the effect of therapy. Not observing an increase in BMD is not evidence of treatment failure. A decrease in vertebral bone mineral density greater than 4-5% indicates a need to evaluate the patient's compliance with therapy and dosing instructions and to search causes of bone loss.
Follow-up and Long-term management for at least 5 years: The most widely used bone medications are the bisphosphonates -- alendronate, risedronate, ibandronate, and zoledronate. Other FDA-approved bone medicines include estrogen or estrogen-progestin hormone therapy, raloxifene, parathyroid hormone, and calcitonin. After initiating a bone medicine, a DXA BMD can be measured in 1 to 2 years to assess changes in bone density. If the bone density is stable or increases, continue therapy. If compliance with treatment has been good and bone density was demonstrated to significantly decrease with treatment, consider a new regimen and reassess bone density in 1 to 2 years. An alternative approach is to measure fasting urinary cross-linked N-telopeptides of type I collagen (NTX) or serum type I collagen C-telopeptides (CTX) before and 3 to 6 months after starting antiresorptive treatment, such as a bisphosphonate. If the marker has decreased by 50% or more, treatment is likely to be successful and bone density can be assessed in 2 years. If the marker has not decreased by 50%, non-compliance or incorrect dosing, such as taking the bisphosphonate with food, is likely causes of a poor marker response (8).
World Health Organization (WHO) and National Osteoporosis Foundation (NOF) algorithm for estimating fracture risk:
In early 2008, the WHO and NOF released a quantitative risk assessment algorithm to guide therapy decisions. New treatment guidelines are based on calculated 10-year absolute risk estimates for fracture. Three variables are of paramount importance in determining risk of osteoporotic fracture: (1) age; (2) BMD; and (3) personal history of previous fracture. Other important factors are: weight and height, history of glucocorticoid therapy, cigarette use, consumption of more than 3 alcoholic drinks per day, history of hip fracture in a parent, history of rheumatoid arthritis, and history of diseases that cause secondary osteoporosis. The new guidelines recommend that therapy be offered to women who are older than 50 years and have a 10-year probability of hip fracture risk greater than or equal to 20%. These threshold levels for treatment are based on a careful assessment of the benefits, risks, and costs of therapy in United States population (9). For postmenopausal women with T-score of -2.5, there are no major changes to previous treatment recommendations. The expert consensus is that those women will benefit from being offered osteoporosis treatment. The major changes will be for women with low bone density (intermediate T-scores). The new risk assessment algorithm and guidelines will likely result in fewer patients younger than 65 years with low bone mass being selected for treatment. Individualization of care remains a cornerstone of osteoporosis treatment. Treat patients with established osteoporosis for at least 5 years. If after 5 years of treatment the patient is at low risk of fracture, consider discontinuing treatment. If the patient continues to be at a high risk of fracture, recommend continued treatment.
Osteonecrosis of the jaw is a rare complication of oral bisphosphonate therapy in postmenopausal women who do not have cancer. For women who have taken a bisphosphonate for 3 years or less, the American Association of Oral and Maxillofacial Surgeons (AAOMS) does not recommend discontinuing treatment prior to invasive dental procedures. However, for women who have taken a bisphosphonate for more than 3 years, the AAOMS recommends cessation of bisphosphonates for 3 month prior to invasive dental surgery. The bisphosphonate can be restarted once the bone has healed (10).
Advances in imaging technology allow clinicians to diagnose osteoporosis before a clinically significant fracture occurs. Numerous therapies are available for the prevention and treatment of osteoporosis in postmenopausal women; however, variations exist in the overall efficacy of these product types, and in the range of skeletal sites at which beneficial effects are observed. Women with low bone density or established osteoporosis should be offered estrogen replacement therapy, alendronate, or calcitonin therapy. Application of these new tools and treatment by obstetrician-gynecologist may reduce the number of osteoporotic fractures experienced by our aging population. It is not only in the area of pharmacotherapies that changes are anticipated within the next few years. Greater emphasis will almost certainly be placed on identification of the determinants of osteoporotic fracture risk, to enable more effective targeting of preventive measures to those women at greatest risk.
- World Health Organization
Prevention and Management of Osteoporosis
- National Institutes of Health
- National Osteoporosis Foundation
Osteoporosis: A debilitating disease that can be prevented and treated
- National Osteoporosis Foundation. Physician's guide to prevention and treatment of osteoporosis. Washington DC: NOF;2003. (Level III)
- Dawson-Hughes B, Tosteson AN, Melton LJ 3rd, et al. National Osteoporosis Foundation Guide Committee. Implications of absolute fracture risk assessment for osteoporosis practice guidelines in the U.S.A. Osteoporosis Int 2008;19:449-458
- Wainwright SA, Marshall LM, Ensrud KE et al. Hip fracture in women without osteoporosis. J Clin Endocrinolo Metab 2005;90:2787-2793
- Bischoff-Ferrari HA, Willett WC, Wong JB et al. Fracture prevention with Vitamin D supplementation: a meta-analysis of randomized controlled trial. JAMA 2005;293:2257-2264
- Siris ES, Chen YT, Abbott TA et al. Bone mineral density thresholds for pharmacological intervention to prevent fractures. Arch Int Med 2004;164:1108-1112
- Leslie WD, Siminoski K, Brown JP. Comparative effects of densitometric and absolute fracture risk classification systems on projected intervention rates in postmenopausal women. J Clin Densitom 2007;10:124-131
- ACOG Practice Bulletin Number. Osteoporosis. Number 50, 2004
- Tosteson AN, Melton LJ 3rd, Dawson-Hughes B et al. National Osteoporosis Foundation Guide Committee. Cost-effective osteoporosis treatment thresholds: The United States perspective. Osteoporosis Int 2008;19:437-447
- Black DM, Schwartz AV, Ensrud KE et al. Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension: a randomized trial. JAMA 2006;296:2927-2938
- ACOG Committee Opinion No. 407. Low bone mass (osteopenia) and fracture risk. Obstet Gynecol 2008;111:1259-1261
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