HORMONE REPLACEMENT THERAPY AND CALCIUM SUPPLEMENTATION

Hormone Replacement Therapy 

Hormone Replacement Therapy (HRT) is the treatment of choice for prevention and treatment of osteoporosis in women. There is no ideal regimen for every woman; therefore, the patient and physician should determine the appropriate prescription for each individual. For maximal skeletal protection, HRT should begin at the time of menopause or oophorectomy, although initiation of HRT any time after menopause has been found to be effective.

Estrogen replacement has been found to decrease bone turnover and prevent bone loss in postmenopausal women. Women exposed to estrogen therapy for seven to ten years or longer have a 50% or greater reduction in the incidence of osteoporotic fractures. Currently, estrogen replacement is available orally or transdermally. A new option of intranasal delivery is currently under study to determine its efficacy in normalizing bone turnover rates.

Estrogen has also been found to retain its positive effect on bone mineral density for many years after menopause, even if considerable bone loss has already occurred. Retrospective studies have shown an approximately 50% reduction in vertebral and hip fractures with full-dosage HRT. Women who once received HRT for more than five years but have discontinued therapy have been found to have up to a 60% reduced risk of hip fracture for up to five years. After five years, the protective effects diminish, but do not disappear altogether.

Additional benefits of HRT include cardiovascular protection; increases in serum high-density lipoprotein along with decreases in serum total cholesterol and low-density lipoproteins; reduced risks of Alzheimer's disease and memory deficits, colon carcinoma, and macular degeneration; reduced oral alveolar bone loss, gingival inflammation and progression of periodontitis; and improvement in menopausal symptoms such as vaginal atrophy, hot flashes and mood changes.

Hormone Replacement Therapy is not without risks or side effects. The most common side effects experienced include hypertension, venous thrombosis, breast soreness, breast cancer, vaginal bleeding, and endometrial disease.

The cause of hypertension with estrogen use is not known. Estrogen, particularly oral administration, has been associated with an increase in both diastolic and systolic blood pressure in about 5% of users. Elevation of blood pressure is rapidly reversed with discontinued use of HRT. Alterations in the route of administration and dosage may alleviate this side effect in some women.

Venous thrombosis has also been identified as an increased risk in women on oral estrogen replacement therapy. The risk of venous thromboembolic event appears to be highest in the first year of treatment and in women with a history of thrombosis. There does not appear to be a relationship between the dosage of estrogen, or between estrogen alone and estrogen with progestin.

To minimize breast tenderness associated with HRT, it has been suggested that gradually increasing the dosage of estrogen and the addition of progestin may be beneficial.

The risk of breast cancer associated with estrogen use has been controversial. Some studies have shown that women who use estrogen five years or less do not have an increased relative risk of developing breast cancer, but those on long-term estrogen use (greater than ten years) have an increase in relative risk of approximately 30%.

Irregular vaginal bleeding can occur in women who have not undergone hysterectomy and who are taking a combined estrogen-progestin regimen. However, this risk decreases with time and usually resolves within six months to one year after initiation of treatment.

Unopposed estrogen therapy (without progesterone) is associated with endometrial hyperplasia in 20% to 60% of users at the end of three years. A woman's risk of developing endometrial cancer with unopposed estrogen use is two to eight times higher than that for the general population. It is generally recognized that the addition of a progestin eliminates or significantly reduces the excess risk of endometrial hyperplasia or endometrial cancer.

The following factors are considered to be contraindications to the use of estrogen or combination estrogen-progestin therapy:

• known or suspected pregnancy; 
• known or suspected breast cancer; 
• known or suspected estrogen-dependent neoplasia; 
• undiagnosed, abnormal vaginal bleeding; 
• active thrombophlebitis, thromboembolitic disorders, or a history of thrombotic disease; 
• hypersensitivity to the hormones; 
• side effects not tolerated by the patient; 
• a substantial and uncontrollable increase in serum triglycerides; and 
• acute liver disease.

Calcium Supplementation 

Calcium is a major component of mineralized tissue and is required for normal growth and development of the skeleton. Optimal calcium intake refers to the levels of consumption that are necessary for an individual to:

• maximize peak adult bone mass, 
• maintain adult bone mass, and 
• minimize bone loss in later years.

Calcium requirements vary throughout and individual's lifetime, with greater needs during the periods of rapid growth in childhood and adolescence, during pregnancy and lactation, and in later adult life. Table 2 lists the current Recommended Dietary Allowances (RDA) for calcium intake.

Table 2.   Current RDA for Calcium Intake

Several factors modify calcium balance and influence bone mass in either a positive or negative manner, thus altering the optimal levels of calcium intake.

1. Vitamin D metabolites enhance calcium absorption by stimulating active transport of calcium in the small intestine and colon. Deficiencies caused by inadequate dietary vitamin D, inadequate exposure to sunlight, impaired activation of vitamin D, or acquired resistance to vitamin D results in reduced calcium absorption. Elderly patients are a particular risk for vitamin D deficiency because of insufficient vitamin D intake from their diet; impaired renal function, which decreases synthesis of vitamin D; and inadequate sunlight exposure, which is normally the major stimulus for vitamin D synthesis. Supplementation of vitamin D intake to provide 600 - 800 IU/day has been shown to improve calcium balance and reduce risk fracture in elderly patients. Sources of vitamin D include sunlight, fortified dairy products, cod liver oil, fatty fish, and supplements. Excessive doses of vitamin D may increase the risks of hypercalciuria and hypercalcemia.
2. Along with calcium intake and intestinal absorption, urinary excretion and fecal loss also influence calcium balance. Intake and absorption account for only 25% of the variance in calcium balance, whereas urinary loss accounts for approximately 50%. A diet high in sodium and animal protein can significantly increase urinary calcium excretion. Excess use of antacid medication may also significantly increase urinary calcium loss.
3. Glucocorticoids, generally used in the treatment of rheumatoid arthritis, inflammatory bowel disease and asthma, can also decrease absorption of calcium. A recent study has shown that calcium and vitamin D supplementation decreases glucocorticoid associated bone loss.

The preferred approach to attaining optimal calcium intake is through dietary sources. Dairy products are the major contributors of dietary calcium. Other good food sources of calcium include green vegetables such as broccoli, kale, turnip green and Chinese cabbage; some legumes; canned fish; seeds; nuts; bread; cereals; and some fortified food products. The Food Guide Pyramid, recommended as the current dietary guidelines by the US Department of Agriculture, includes two to three servings per day of dairy products and three to five servings of vegetables.

Calcium supplements may be the preferred way to attain optimal calcium intake, and should be recommended in the context of the total diet. Calcium supplements are available as various salts. Absorption of calcium supplements is most efficient at individual doses of 500mg or less and when taken between meals. However, calcium carbonate absorption is decreased in fasted individuals with an absence of gastric acid, and should be taken with certain food. Calcium citrate does not require gastric acid for optimal absorption and is recommended in older individuals with reduced gastric acid production.

The most common side effect of calcium supplementation is constipation. Calcium toxicity, with high blood calcium levels, severe renal damage, and ectopic deposition can be produced by overuse of calcium carbonate. Caution is recommended in individuals who have a history of kidney stones, because high calcium intake can increase urinary calcium excretion and may increase the risk of stone formation.