Pharmacotherapeutics for Osteoporosis Prevention and Treatment

Michele R. Davidson, CNM, PhD

Disclosures

J Midwifery Womens Health. 2003;48(1) 

In This Article

Risk Factors for Osteoporosis

Postmenopausal women represent the most common risk group for osteoporosis. Decreased levels of estrogen, which occur from either natural or surgically induced menopause, lead to acceleration in bone loss. It is estimated that 21% to 30% of Caucasian, postmenopausal women have osteoporosis, and an additional 54% have low bone mass, causing susceptibility to both osteoporosis and risk of fractures later in life.[4] Previously, it was believed that estrogen replacement therapy (ERT) and hormone replacement therapy (HRT) both prevented and treated osteoporosis. New findings indicate that although ERT/HRT may prevent osteoporosis by decreasing the rate of bone loss, there is no evidence that it is effective for treatment of osteoporosis.[8] The Food and Drug Administration (FDA) recently required that the indication labeling on HRT products be changed from a treatment and preventative therapy to a preventative therapy only.[7] In May 2002, the authors of the Women's Health Initiative, a randomized controlled primary prevention trial of 16,608 women, recommended that the study be stopped 3 years early and that HRT not be prescribed for long-term prevention of chronic diseases.[9] Although the study demonstrated a reduction in observed hip and clinical vertebral fracture rates by one third compared to placebo, the Women's Health Initiative authors recommend the use of alternative preventive and treatment strategies for osteoporosis to avoid the increased significant risk of breast cancer for which the Women's Health Initiative was stopped at 5.2 years (planned duration, 8.5 years).[9]

Combined oral contraceptive pills appear to have protective bone benefits to users.[10,11] Oral contraceptives used for perimenopausal symptoms in the fourth decade of life offer relief from vasomotor symptoms in addition to estrogen supplementation to decrease bone loss that can occur when estrogen levels begin to fall.

Personal Medical History and Family History

Personal and family histories are key components that may alert a woman and her clinician to an increased risk for osteoporosis. Women with a history of previous fractures should undergo bone mineral density testing to evaluate the status of their bone mass. Certain medical conditions can also predispose an individual to a loss in bone mass, which can lead to osteoporosis. Hormonal abnormalities, such as hyperthyroidism, and hyperparathyroidism can impair the bone-making process. Individuals with a history of neoplastic disorders, such as multiple myeloma, are also at risk. Individuals with metabolic disorders, such as osteomalacia, or connective tissue diseases (osteogenesis imperfecta) should also be screened.[2,3] Most individuals with these conditions will already be receiving care from a specialist; however, it is important to ensure that the woman is receiving proper medical screening and treatment. Women with these disorders who have not been screened for osteoporosis should be referred to a specialist for follow-up care. Nutritional deficiencies, such as inadequate calcium or vitamin D intake, are additional risk factors that should be assessed.[5] In addition, women with a family history of osteoporosis or of fractures that have occurred in first-degree relatives are also at an increased risk for the disease.[2] Both modifiable and non-modifiable risk factors for osteoporosis are listed in Table 1 . .

Factors that are protective and associated with a decreased risk of osteoporosis include high parity (because pregnancy is a high-estrogen state), large body habitus, and history of moderate exercise.[10] During breastfeeding there is a depletion of estrogen; however, the bone loss that occurs is regained after nursing is discontinued.[11,12,13] Even multiparous women who have breastfed for an extended period of time do not appear to have a significant decrease in bone mineral density when compared with women who breastfed for shorter times.[14] Karlsson and colleague.[12] compared average bone mineral density measurements of 73 lactating postpartum women with the bone mineral density measurements of 55 age-matched women who served as controls. A subgroup of 39 multiparous women with greater than four births was compared with a control group that consisted of 58 premenopausal women who had a maximum of two births. The results were controlled for differences in total fat mass and total lean mass. Lumbar bone mineral density was 7.6% ± 0.1% and total bone mineral density was 3.9 ± 0.1% lower in women postpartum than in the control group (P < .001). Mothers who were breastfeeding for a duration of 1 to 5 months decreased femoral neck bone mineral density by 2.0% ± 1.0% during the first 5 months postpartum; however, no additional bone mineral density loss was seen during 6 to 12 months in lactating women (P = .05). Women in the subgroup with at least four deliveries did not show a significant difference in bone mineral density compared with the women with only two deliveries. Total duration of lactation was not correlated with present bone mineral density. Extended lactation and multiple pregnancies did not increase a woman's risk of osteoporosis.[12] Although bone mineral density and calcium levels decline during lactation, transient bone loss normalizes after weaning.[12] The risk for older women who become pregnant, breastfeed, and then quickly enter menopause are less clear. Some studies have revealed that parity in itself is protective against osteoporosis. Bone mineral densities in postmenopausal multiparous women increased with the number of births until age 69.[13] Fractures occurred more commonly in nulliparous women and in women over the age of 70. These findings may impact clinical decisions in recommending hormone replacement as well as counseling women on the protective benefit of pregnancy.[14]

Age and Risk of Osteoporosis

Age is the most important risk factor for osteoporotic fractures. Women, especially elderly women, in poor health, those with dementia, or those with poor uncorrected eyesight have a higher risk for falls or fractures.[2,15] Although osteoporosis occurs most commonly in postmenopausal women, it is occurring more frequently in adolescent girls, especially young female athletes who participate in endurance activities such as gymnastics, ice-skating, and dance. These girls are prone to fractures due to low bone mineral density, overtraining, and vigorous dieting practices.[2] Some young athletes experience multiple health problems including eating disorders, amenorrhea, and low bone mass. Young women who experience this cluster of symptoms known as the "female athletic triad" (eating disorders, amenorrhea, and low bone mass) may permanently lose their opportunity to establish a healthy bone mass, thus increasing their risk for osteoporosis and fractures in later life.[2,4,16] The peak bone mass for all persons is achieved during the adolescent years, a crucial time for bone growth. Ninety-eight percent of the skeletal mass is acquired by age 20.[1] Gradual loss of bone starts to occur sometime between the ages of 30 and 40. For women, rapid bone loss accelerates at the time of menopause with a loss of 2% to 5% over the next 10 years.[7] The need for a well-balanced diet and physical activity are essential to tissue and bone growth. Adolescence is also a time when lifelong health promotion habits are forming. Counseling should focus on healthy eating patterns, promotion of physical activity, and reaching or maintaining an appropriate weight range for young women.

Role of Lifestyle Factors in Risk for Osteoporosis

A sedentary lifestyle, cigarette smoking, and excessive alcohol intakes are lifestyle factors associated with an increased risk for osteoporosis. Clinicians can identify these risks and provide educational teaching to decrease both risk factors and environmental hazards.

Pharmacologic Risk Factors

Certain medications may put individuals at risk for a reduction in bone mass.[17,18] Phenytoin sodium (Dilantin) is an example of an anticonvulsant that can predispose an individual to osteoporosis when used for long-term management. Glucocorticoids have a negative impact on the bone formation process. They reduce bone formation by decreasing the osteoid thickness, the mineral apposition rate, the rate of bone mineralization, and the osteoblast activity. High doses may also lead to trabecular thinning and a loss of trabecular connectivity.[18] This can result in fractures of the pelvis, vertebrae, and ribs. These drugs also decrease uptake of vitamin D in the intestinal tract, which leads to an increase in renal calcium secretion.[7] Sachs reviewed the effects of glucocorticoid administration in asthmatic children and found that 46% suffered from osteopenia.[17] Glucocorticoid medications are commonly used to treat asthma, inflammatory disorders, cystic fibrosis, chronic obstructive pulmonary diseases, as well as patients who have received transplants.[7,18,19] The use of these drugs accounts for 25% of the cases of osteoporosis. Individuals taking these drugs often have other risk factors, such as elderly age, postmenopausal status, smoking, sedentary lifestyle, and malnutrition.[7,19]

Medroxyprogesterone acetate (Depo-Provera) also may increase bone resorption because it induces a hypoestrogenic state. Studies have yielded mixed findings on the effects this drug has on bone mineral density. Bahamondes and colleague.[20] compared bone mineral density in 50 premenopausal women who had never used hormonal contraception with 50 premenopausal women who had used Depo-Provera for at least 1 year. Bone mineral density was significantly lower in the group who were currently receiving Depo-Provera. Although bone mineral density was lower, the authors stated they could not conclude that Depo-Provera users were at risk for osteoporosis. Another study compared the bone mineral density in women aged 30 to 34 years of age; Depo-Provera users, oral contraceptive users, and women who had never used hormonal contraceptives. Study results did not find a difference in the three groups when bone mineral density was measured.[21] The practice of prescribing Depo-Provera (depo-medroxyprogesterone acetate) to young adolescents (<16 years of age) for prolonged periods of time (e.g., >5 years) may warrant caution because these young women have not yet reached peak bone mass.[22]

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