Osteoporosis

Laird Madison, M.D.

Osteoporosis is a common disease of decreased bone mass which results in micro architectural deterioration and an increased susceptibility to fractures. The rationale for diagnosing and treating osteoporosis is to reduce the risk of future fractures. The disease itself produces no signs or symptoms until fracture occurs. Recent developments in diagnostic techniques, a new appreciation of the skeletal and non-skeletal benefits of post-menopausal estrogen therapy, and several new non-estrogen therapies for osteoporosis have greatly renewed interest in the disease among physicians and patients. Fractures, especially of the hip, result in a profound amount of morbidity and mortality in older adults.

Epidemiology

Bone density is a function of genetic, racial, age-related, life-style, and co-morbid disease related factors. Among these, race and age are probably the most significant. Men have significantly higher bone mineral density (BMD) and a consequent lower lifetime risk of fracture. Low bone density resulting in increased fractures is seen most commonly in female Caucasian and Asian elderly. An individual's peak BMD occurs around age 35. After a 10 year plateau, by age 45, a progressive decline begins in bone density of ~1%/year. Variables which influence this pattern include an accelerated loss in women following the post-menopausal loss of estrogen, co-morbid disease, and lifestyle related factors which reduce peak bone density or accelerate loss during the age related decline.

The lifetime risk of fracture for a women reaching age 55 is ~40%. By the end of the first post-menopausal decade approximately one-half of the US female population meets the diagnostic criteria of osteoporosis, which is a BMD more than 2.5 Std. Dev. below the mean peak BMD of same sex and race, healthy, young adults. The decision to base the comparison of an individuals BMD against young controls (T score) as opposed to age-matched controls (Z score) may seem unsound, however because the incidence of the disease in the population is so large, age-matched controls are not clinically useful. The predictive epidemiological data relating BMD to future fracture risk is based on young healthy adult BMD
(T score) comparisons only.

Risk Factors for Osteoporosis

Female sex

Caucasian or Asian race

Tall stature and/or small frame

Family history

Advanced age

Early menopause

Hypogonadism prior to menopause

Hyperthyroidism

Hyperparathyroidism

Prolonged immobility

Chronic renal failure

Hepatic disease and malabsorption syndromes

Steroid use

Smoking and alcohol consumption

Anti-convulsant therapy

Diabetes mellitus

Life-long low intake of calcium and Vitamin D

Clinical Evaluation and Diagnostic Assessment

History:

Review of risk factors for both primary and secondary causes of osteoporosis above), dietary assessment of Vit. D and calcium intake, history of fractures, decrease from peak adult height, family history.

Physical Exam:

Height, weight, body stature, body height < arm span, kyphosis.

Laboratory:

CBC, serum chemistries (calcium, phosphate, liver enzymes, total alkaline phosphatase, creatinine, electrolytes), urinalysis, including pH. If history or initial labs warrant: TSH, 24 hr. urine calcium, PTH, 25 OH Vit D, serum protein electrophoresis, acid-base studies.

Bone Densitometry:

BMD measurement is indicated whenever a clinical decision to intervene with a therapeutic agent will be influenced by the result. DEXA measurement of the lumbar spine and hip is the most precise and accurate technique. Measurement of BMD at lumbar vertebrae is most sensitive to changes, while measurement at the hip gives information about the most critical site for fracture. Discrepancy between BMD measurements at different sites are not unusual and reflect true differences in density BMD at the lumbar vertebrae is subject to several artifacts which can raise the measured BMD (osteophytes, aortic calcification, etc.). Calcaneal ultrasound measurement of bone density is a new effective technology for screening for osteoporosis. It is probably not sensitive enough for accurate determination of severity or for following the response to therapy.

Decision-Making Process

Although bone mass is the single best predictor of fracture risk, other factors influence an individual patient's fracture risk. Even patients with the lowest BMD can remain fracture free. Alternatively, patients with an existing fracture are at higher risk for subsequent fracture regardless of their BMD. The decision to intervene therapeutically should be based on a global profile of the patient and not just the BMD. A significant variable is the patient's acceptance of the proposed treatment, especially estrogen therapy, which requires a patient's understanding of both the risks and benefits. Additionally important variables are the patient's activity level anticipated compliance, lifestyle, a history of previous fractures, and a maternal history of hip fracture.

Treatment

Diet:

Adequate consumption of Vit. D and calcium will not prevent or effectively treat osteoporosis, but is essential for any effective treatment of osteoporosis. Elderly and institutionalized patients commonly have inadequate daily consumption, which can result in secondary hyperparathyroidism, osteomalacia and increased fracture risk on this basis alone. Three 8 oz. glasses of milk provides adequate calcium and Vit. D. Other dairy products provide large amounts of calcium but are not supplemented with vitamin D. Intake of 1,000 to 1,500 mg calcium/day can be provided by a variety of commercially available tablets or with generic calcium carbonate (antacid) tablets. Vitamin D (400 IU/day) can be included in the calcium tablets or taken in the form of a daily multi-vitamin. Patients with hypercalcuria (e.g. hyperparathyroidism) should not receive and calcium or Vit. D supplementation.

Activity:

Encourage weight bearing exercise, discourage alcohol and tobacco consumption, reduce risk of falls through home environment modification (anchor rugs, handrails, etc.), avoid other drugs which can slow reflexes or impair coordination and contribute to falls.

Estrogen:

The therapeutic benefits of estrogen replacement following menopause are well established and include important health benefiting effects in addition to preservation of skeletal mass (cardiovascular, CNS). A progestin should be given concomitantly or in a cyclic pattern if the woman has not had a hysterectomy. Risks: mastalgia, intermittent uterine bleeding (spotting), slight increased risk of breast cancer, doubling of risk for cholelithiasis. Contraindications: known or suspected cancer of the breast or uterus, abnormal or undiagnosed genital bleeding, active thrombophlebitis or a history of thrombotic disease. Duration of therapy: the beneficial effects of estrogen are most profound in the 10-20 year period following the menopause and may have less of a beneficial effect for women older than 75 who can experience age-related bone loss while on estrogen therapy. Increased bone loss resumes after estrogen is discontinued at any age. In the absence of a contraindication estrogen therapy can be continued for life.

SERMs:

A new class of molecules, termed Selective Estrogen Response Modifiers, offers additional flexibility for replacing estrogen in post-menopausal women. These compounds have tissue specific mixed agonist/antagonist effects. Raloxifene has been approved for the prevention of osteoporosis in peri-menopausal women. It acts as an estrogen agonist in bone and the liver, producing increases in bone density and a favorable estrogen-like change in lipid profile. It has been documented to reduce the incidence of breast cancer, which reflects the antagonist action of the compound at the breast. Unlike tamoxifen, the compound does not cause endometrial hyperplasia.

Testosterone:

Men should receive replacement testosterone therapy at any age for hypogonadism. Ongoing evaluation for benign prostatic hypertrophy and prostate cancer is appropriate for any man receiving testosterone supplements.

Bisphosphonates:

Alendronate has been approved for the treatment of established osteoporosis in post-menopausal women. It is an effective alternative in women who cannot or will not take estrogen. Its efficacy in preventing osteoporosis at the start of menopause has not yet been established, but is so likely, that its use in newly menopausal women with additional risk factors is common. The drug is poorly absorbed and must be taken on an empty stomach, in the morning, with tap water only. The recommended dose is 10mg per day. Incidents of esophageal irritation and erosion have occurred in patients with gastro-esophageal reflux who were supine following ingestion. Concomitant therapy with adequate Vit. D and calcium is mandatory. Treatment for three years has been shown to increase hip BMD by 5-8% and reduce new vertebral fractures by 50%.

Calcitonin:

A nasal spray formulation of Salmon calcitonin is also approved for treatment of post-menopausal osteoporosis in woman. The recommended dose is 200 U by intranasal spray every day. Calcitonin has an analgesic effect in many patients and is particularly useful in the immediate post-fracture period. The effects on BMD are less dramatic than with bisphosphonates, and may not be sustained beyond 1-3 years. There is less data concerning the reduction fracture risk with calcitonin than with alendronate.

Exercise:

A regular program of weight bearing exercise is very beneficial for reducing risk of fracture by maintaining BMD and improving muscle strength and balance. For less capable patients, physical therapy can help reduce fracture risk from falls in patients. A physical therapist-directed program to improve muscle strength, posture, and balance is often indicated in patients with established osteoporosis.

Continued Assessment:

Estrogen therapy mandates an ongoing assessment of associated risks, including pelvic examination, breast examination, mammography, and PAP smear on a yearly basis. Anti-resorptive agent therapy with alendronate or calcitonin generally requires no laboratory monitoring of effectiveness or side-effects. However, follow up assessment of bone resorption markers with urinary measures of specific collagen breakdown products may be useful to assure patient compliance and provide both the physician and the patient with early evidence of successful therapeutic intervention. Follow-up BMD at yearly intervals is indicated until BMD stabilizes after which bi-annual measures are adequate. For women not receiving therapy who had adequate BMD levels at initial evaluation, reassessment at 2-3 year intervals is appropriate.