Health Conditions

What is on the horizon?

With the number of individuals who have osteoporosis expected to increase dramatically as members of the large post-World War II generation reach old age, researchers are taking several approaches to prevent and treat this condition.

First, studies are underway to develop methods of detecting osteoporosis earlier. Earlier treatment may prevent or lessen the risk of fractures as well as other results of osteoporosis (such as decreased height and rounded back).

Bone density of older adults depends on the total amount of bone acquired during growth. One study that is currently being conducted tests whether implementing a specific bone-building program during childhood will increase the development of both bone density and the amount of calcium and other minerals in bones. Although bones are strengthened for the whole body, special emphasis is placed on the spine, thigh bone at the hip, and forearm at the wrist, which are the areas most at risk for fractures due to osteoporosis. Additionally, specific types of exercises are being evaluated for their potential to enhance the formation of thicker, stronger bone at an early age.

The effects of vitamin supplementation ? in particular vitamin A - are also under study. Although one recent study reinforces previous findings that men with high levels of vitamin A in their bodies are at the highest risk for fractures, other study evidence finds no association between osteoporosis and vitamin A.

A group of Swiss researchers recently studied the effects of potassium citrate on bone density. The study suggested that taking the supplement may help to partially neutralize high levels of acid that are common in modern diets and can lead to increased bone density in postmenopausal women with osteopenia. While news of the effects of potassium citrate on bone density are promising, it's too early to recommend its widespread use for prevention or treatment of osteoporosis. Future research will likely examine the effects of potassium citrate on fracture rates.

Natural foods, such as soy, contain phytoestrogens (plant-produced substances that act like estrogen in the body). In general, individuals who consume diets high in phytoestrogens ? particularly phytoestrogens that belong to the subgroup of isoflavones - seem to maintain bone density. Therefore, isoflavones are of interest as potential osteoporosis prevention. Much more long-term controlled research is needed to prove a bone-saving effect for them, though.

Although lifestyle and environmental factors play important roles in delaying or preventing osteoporosis, for an estimated 50% to 90% of individuals, bone mineral density is determined primarily by heredity. Therefore, researchers are also trying to approach treatment and prevention of osteoporosis through isolation of the gene or genes responsible for osteoporosis. Currently, genetic research for osteoporosis takes two tracks. First, researchers are working to determine what specific genes may play a key role in determining and maintaining bone density. A second focus is to identify genetic differences in natural body receptors that may contribute to decreased bone density. Current research centers on estrogen receptors alpha (ERS1s) and vitamin D receptors (VDRs), but several other receptor types are also being studied.

Potential new drug therapies for osteoporosis include some medications already approved for other conditions.

Most notable are hydroxymethylglutaryl-coenzyme-A reductase (HMG Co-A) inhibitors ? commonly called ?statins". A class of drugs used to lower cholesterol levels, statins have recently received considerable attention for the possible treatment of osteoporosis. In some laboratory studies of animals and observational studies of humans, statins have appeared to increase bone density. Because common steps occur in both the formation of cholesterol and the activation of osteoclasts, statins may disrupt both activities by blocking certain key steps. However, these findings are very preliminary and more studies will need to be conducted before recommendations on using statins for osteoporosis can be made.

Sodium fluoride, a drug commonly used to prevent tooth decay for children, may also have benefits in building and/or maintaining bone. Results from long-term studies ? primarily in postmenopausal women ? have been inconclusive, however, with some studies showing that fluoride may increase bone density, and others showing little or no effects on bone.

Growth hormone (GH) deficiencies are associated with lower-than-average bone density in adults who are GH deficient or who were GH deficient as children. Supplemental GH increases the rate of bone "turnover" (the replacement of old bone cells with new ones). Soon after GH therapy is started, bone density may actually decrease as old bone is broken down faster. Over a longer time, however, the formation of new bone usually accelerates and bone density may increase.

New agents are under study among drug classes already being used to prevent or treat osteoporosis. New bisphosphonates that are in development ? such as clodronate and minodronate ? may need fewer doses, have different dosing schedules, and come in different dosage forms. PTH is also being developed in non-injected forms, such as transdermal patches. SERMs under study for treating osteoporosis include arzoxifene, bazedoxifene, lasofoxifene, and opsemifene. Because many SERMs seem to reduce the chance of getting breast cancer for women using them for osteoporosis, SERMs are also being studied for preventing breast cancer. They may also have cholesterol-lowering effects. Also under study is combination therapy involving treatment with an agent that builds bone (such as PTH) followed by a drug like a bisphosphonate or a SERM that lessens bone loss.

Potential new classes of drugs for preventing and/or treating osteoporosis include both agents that decrease or delay the rate of bone break down (anti-resorptive agents) and those that increase or speed up the rate of bone formation (anabolic agents). Some investigational agents may do both and some may offer additional health benefits, as well. Among some of the drug classes under various stages of investigation are:

Bisphosphonate esters (BPEs) - are a class of drugs that limit the activity of osteoclasts, like bisphosphonates do. However, BPEs also seem to increase the activity of osteoblasts; so they may actually cause bone density to increase.

Cathepsin K inhibitors ? A type of enzyme that breaks down a body protein known as cysteine, cathepsin K is believed to activate osteoclasts. Agents that block the effects of cathepsin K may slow down bone resorption while bone formation continues at a normal rate.

Insulin-like growth factor-1 (IGF-1) ? a substance produced in the liver, IGF-1 is stored in bone. Released during bone break down, it encourages the production of osteoblasts to rebuild bone cells. IGF-1 deficiencies have been associated with lower-than-expected bone density and an increased risk of osteoporosis-related fractures.

Integrin receptor inhibitors (also called disintergins) ? Investigational drugs in this class (including contortrostatin, echistatin, and SC56631) block the attachment of osteoclasts to bone. Osteoclasts are prevented from beginning the process of bone break down. Integrin receptor inhibitors may also prevent or slow down the production of osteoclasts, thereby decreasing the number of osteoclasts available to break down bone. Of particular interest are integrin alphavbeta3 receptors, which may also be called vitronectin receptors.

Nitrosylated non-steroidal anti-inflammatory drugs (NO-NSAIDs) ? Certain pain-relievers known as NSAIDs (such as flurbiprofen) may be modified to release nitric oxide (NO) in the body. NO, a byproduct of body processes, has many potential effects. In particular, low levels of NO are associated with increased bone break down, but high levels of NO seem to lessen the rate of bone resorption. In theory, increasing amounts of NO in the body could help to prevent and/or treat osteoporosis.

Osteoprotegerin (OPG) ? OPG is a cytokine (a protein produced within the immune system to help control immune function). Laboratory animals with low levels of OPG also tend to have faster bone turnover, poor attachment of new bone cells to old cells, and a less stable bone structure. Increasing OPG may help to normalize bone turnover.

Src inhibitors ? By limiting the effectiveness of Src tyrosine kinase (STK), an enzyme that triggers osteoclast activity and inhibits osteoblasts, Src inhibitors are thought to lessen bone break down and encourage bone formation.

Strontium ranelate - An oral drug, which has been tested in laboratory studies and at least two large studies of postmenopausal women with osteoporosis, strontium ranelate appears to decrease the rate of bone break down. It also increases the rate of bone formation. Using it may actually restore lost bone density, if bone-building osteoblast activity replaces bone cells faster than osteoclasts break down bone. Strontium ranelate was recently approved for us in Europe, but is not currently approved by the FDA.

Tibolone ? A steroid usually described as ?tissue-specific?, tibolone concentrates in certain body tissues, such as bone, where it acts like estrogen to maintain bone density. Although it does not have estrogen-like effects on the breasts or uterus, tibolone may also reduce hot flashes and other symptoms of menopause. Tibolone is already approved for use in several countries, but not yet in the United States. Long-term studies are underway to evaluate its possible side effects.