Osteoporosis Prevention, Diagnosis, and Therapy
What?
Who?
Consensus Reference:
Controversy
Recommendation
Future
Estimating Risk

Backdrop: An estimated 10 million Americans suffer from osteoporosis; another 18 million have bone mass low enough for them to be considered at risk of the disorder. Among elderly persons, a fracture (Fx) can have devastating consequences-surveys indicate 80% of women over 75 "would rather be dead than have a bad hip fracture."

Candidates
· Post-Menopausal Women
· Women, prior to the normal age of menopause (age 52-58 in N. America), without exogenous estrogen, e.g., oophorectomy
· Males with anti-testosterone Rx (e.g., GNRH (Lupron)

Discriminating Variables
- X-ray showing osteopenia
- History (Hx) Fx(s) e.g. Stress, Vertebral Crush, Colles' Fx
- Structural findings, e.g., Kyphosis; loss height
- Family Hx (FHx) osteoporosis
- Ch. Steroids (Tx course(s) > 3wks)
- Hyperthyroidism, Hypercorticalism, Hyperparathyroidism, Hyperprolactinemia, Hypogonadism; Ch. Renal Failure, COPD, DM, Hepatic disease, Immobility, Malabsorption, Ontogenesis Imperfecta, Osteomalacia, RA, Sarcoidosis, Scurvy, Systemic Mastocytosis
- decreased PTH function - decreased calcium intake/absorption
- Known Type I (age 51-75; 6:1 female to male; accelerated bone loss; decreased PTH - Known Type II (age>70; 2:1 female to male; not accelerated bone loss; increased PTH - Vegan > 10yrs, postmenaupausal
- Rx that can cause bone change such as alcohol, Aluminum containing antacids, barbiturates, Corticosteroids, Dilantin (Phenytoin), Heparin, Isoniazid, MTX, L-thyroxine, Tobacco

Abnormal: 1 SD below mean If between mean and that, repeat the testing in 2-5 yrs.

NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy March 27-29, 2000.Vol. 17, No. 1 as referenced in JAMA 

NIH Osteoporosis and Related Bone Disease, National Resource Center Report

• The full bibliography is available and it includes:
  What Is Osteoporosis and What Are Its Consequences?
  How Do Risks Vary Among Different Segments of the Population?
  What Factors Are Involved in Building and Maintaining Skeletal Health Throughout Life?
  What Is the Optimal Evaluation and Treatment of Osteoporosis and Fractures?

Controversy: There are two types of bone density examinations have been shown to detect increased risk of osteoporotic fracture:
1. Ultrasound on the heel
2. An X-ray of the femur just below the hip.

However, among women between 50 and 59 years of age, it is estimated that 750 bone mineral density (BMD) tests would be required to prevent a single fracture over a period of 5 years.

Recommendations: Therefore (and, don't kill the messenger), a NIH consensus panel (March, 2,000) said too little is known about the benefits of mass screenings to recommend them. "We need to learn more about screening, which population should be screened and how to best do this," said the Panel's Chair, Anne Klibanski. They offered that doctors and their patients should decide on case-by-case basis, and they failed to recommend a guideline.
- Although hormone replacement therapy (HRT) is a common treatment (Tx), the Panel said more information is needed on how estrogen alone or in combination with other drugs reduces the incidence of Fx's.
- Newer drugs, including bisphosphonates, have been shown to increase bone density.
  E.G., those women with the greatest loss of BMD loss at baseline, enjoyed the greatest gains during continued Tx; initial gains are easier to achieve than later one, naturally. Specifically, among women taking alendronate whose hip BMD decreased by more than 4% during the first year, 83% (95% CI, 82%-84%) had increases in hip BMD during the second year, with an overall mean increase of 4.7%. In contrast, those who seemed to gain at least 8% during the first year lost an ave. of 1% (95% CI, 0.1%-1.9%) during the next year. Similar results were observed among women taking raloxifene for 2 years.
- There is no evidence that so-called "natural estrogens" found in food supplements and some plant products, such as soy, reduce osteoporotic fractures.
- Weight training, even in elderly persons, increases bone mass. Non-impact exercise, such as walking, does not build stronger bones but may be valuable in improving balance and preventing falls.
- The panel called for increased emphasis on diet and exercise among children, noting that only about 25% of boys and 10% of girls between the ages of 9 and 17 meet the National Academy of Science recommendations for daily calcium intake.
JAMA. 2000;283:1318-1321

Three-year Study: risedronate compared with placebo. Tx'd women initially received either 2.5 or 5 mg daily, but the 2.5-mg arm of the study was discontinued after 1 yr. All women also took 1,000 mg of calcium daily, and those who had low levels of 25-hydroxyvitamin D took up to 500 IU/day of it. After only 1 year of Tx, fracture risk was reduced by 65% in women taking 5 mg/day risedronate compared with controls. After 3 years, the cumulative incidence of new vertebral Fx was reduced by 41%, and the incidence of non-vertebral fractures was reduced by 39% in the 5 mg/day-risedronate group compared with controls. It also resulted in significant bone mineral density increases at the lumbar spine, femoral neck, femoral trochanter and midshaft of the radius.
JAMA 1999;282:1344-1352.

Parathyroid hormone (PTH) was 3X more effective than available drugs at reversing the bone loss associated with osteoporosis. In a study, about 2/3 of postmenaupausal women on estrogen Tx who were also treated with PTH increased bone mass in their vertebrae or backbones by 30%. In 64% of the women taking parathyroid hormone, bone mass was restored to pre-osteoporosis levels and compares "very favorably with estrogen and alendronate and other therapies that act primarily to suppress bone resorption," or the loss of bone density."
Dr. Chris Arnaud (Sr. investigator, University of California, San Francisco, as reported by Reuters Health, 1999-06-18. [Parathyroid hormone helps reverse osteoporosis 1999-06-16 Addition of parathyroid to estrogen called "an approach to a cure" for osteoporosis 1999-06-16]

Future: While current drugs for osteoporosis may be somewhat effective in stabilizing bone mass and preventing further bone loss, patients who have the condition have already lost half or more of their bone mass in critical skeletal sites, on average. Therefore the holy grail would be a drug that rebuilds bone that's already disolved. That may be the statins, found to reverse bone loss in mice after screening 30,000 natural compounds to find a small molecule that could activate expression of the bone morphogenetic protein-2 gene in mouse osteoblast cells. This gene was chosen because this family of genes is known to enhance osteoblast differentiation.
G Mundy, Science 1999;286:1946-1949.

Consensus Panel Considers Osteoporosis from Doctor's Guide

Osteoporosis Risk Estimation
"4 decision rules Simple Calculated Osteoporosis Risk Estimation (SCORE), Osteoporosis Risk Assessment Instrument (ORAI), Age, Body Size, No Estrogen (ABONE), and body weight less than 70 kg (weight criterion) for selecting women for dual-energy x-ray absorptiometry (DXA) testing and to compare results with recommendations made in the National Osteoporosis Foundation (NOF) practice guidelines." "DXA testing is important for evaluating the severity of bone loss and making treatment decisions. The ABONE and weight criterion decision rules miss 13% to 17% of women with osteoporosis and are thus not useful case-finding approaches for DXA testing. The SCORE and the ORAI, however, are better than the NOF guidelines, targeting testing on women at high-risk for low BMD. The acceptability of these rules in clinical practice merits further investigation. Future research should include a cost-effectiveness analysis to identify acceptable sensitivity and specificity, and an impact assessment to evaluate the utility of these decision rules in clinical practice." Cadarette SM, Jaglal SB, Murray TM. Evaluation of Decision Rules for Referring Women for Bone Densitometry by Dual-Energy X-ray Absorptiometry JAMA July 4, 2001;286(1)