Bisphosphonates, Prolia & Forteo in Osteoporosis Treatment

When I started practicing clinical medicine in South Florida there were few if any treatments for osteoporosis. We saw the devastating effects of this condition in lean post-menopausal women in their seventies and eighties – especially those who had multiple pregnancies and smoked. In men we were more likely to see it in male smokers taking corticosteroids for an inflammatory disease.

Spontaneous collapse of their vertebrae leading to nerve compressions, brutal unrelenting pain and at times neuromuscular injuries preventing walking were common. If we measured height, we saw a decrease in height over time before these catastrophic spinal injuries occurred. We also saw a plethora of spontaneous hip fractures which occurred causing a fall with trauma. In most cases, both presentations resulted in major and extensive surgery and rehabilitation before a patient resumed their life. The only medications we had at the time for women were estrogen and progesterone which carried their own list of potential adverse effects.

The introduction of oral bisphosphonates changed that. Medications like Fosamax, Actonel, Boniva slowed down the process and, with weight bearing exercise, smoking cessation, appropriate nutrition, and luck, reversed it. These medications in pill form were tough to take and still are. They are large, poorly absorbable and require you to take them on an empty stomach while upright. Most instructions call for drinking eight ounces of water with the pill followed by another eight ounces of water after the pill then staying upright for 30-60 minutes. These pills are extremely corrosive if they get caught in your esophagus because you didn’t swallow them with water. They can upset the gastric lining of your stomach as well.

Bone Densitometry tests allowed physicians to detect and then follow serially over years the thickness of your bones. I believe due to the size of the pills and the gastrointestinal problems they can cause convincing patients to try these medications has always been a difficult prospect. Fortunately, much of the responsibility falls on the gynecologists who look for osteoporosis and osteopenia as part of their evaluation of perimenopausal women routinely.

For those individuals unable to tolerate these oral medications, or unwilling to try, rheumatologists have injectables to help the bones. Prolia (denosumab) an injectable given every six months, and Forteo, (teriparatide) a daily injectable, were developed. They too can produce side effects including back and bone pain and a host of others. The good news is they work.

In a recent study of 50,862 women published in the journal Therapeutic Advances in Musculoskeletal Diseases researchers from the University of Verona, Italy led by Giovanni Adami, found that the oral medications can reduce the risk of fracture by 30% while monthly Prolia did so by 60% and daily Forteo by 90%. The significant difference was the fact that the oral agents required one year of use before the risk of a spontaneous fracture occurred while the injectables achieved success much sooner. While rheumatologists and gynecologists surmised this was occurring, this study provides solid evidence to back up their hunches.

“Buyer Beware”- Supplements Are Not What They Are Advertised to Be

According to an article authored by Maria Elena Martinez’s (Ph.D., University of California, San Diego) in the Journal of the National Cancer Institute, “Consumers need more information and guidance about the risks as well as the benefits, of using dietary supplements for cancer prevention.” Dr. Martinez states that dietary supplements have little supporting evidence for health benefits in disease prevention – particularly cancer.

“Despite this evidence, marketing claims by the supplement industry continue to imply anti-cancer benefits“ Martinez wrote.  “Insufficient government regulation of the marketing of dietary supplement products may continue to result in unsound advice to consumers. Both the scientific community and government regulators need to provide clear guidance to the public about the use of dietary supplements to lower cancer risk.”

Half of US adults use one or more daily dietary supplements. “Use of supplements has been fueled primarily by marketing oriented claims of wide ranging benefits,” Martinez and her co-authors wrote. “As a result, sales of dietary supplements have grown into a $30 billion a year industry.”

To assess the current status of evidence supporting use of supplements, Martinez and her associates reviewed literature for supplements that have been tested in adequately powered clinical trials or in large, well-designed observational studies.  The review looked at data for the use of antioxidants, folic acid, Vitamin D and calcium to prevent cancer.

Preclinical studies suggested that dietary antioxidants including beta carotene, alpha tocopherol, and Vitamin C encouraged growth of normal cells and tissue and inhibit growth of abnormal tissue. Clinical studies failed to support those ideas:

>  Beta carotene did not prevent recurrence of non melanoma skin cancer

>  Beta carotene, alpha tocopherol and Vitamin C failed to prevent recurrence of colonic adenomas

>  Beta carotene, Vitamin A and alpha tocopherol did not prevent lung cancer

>  Vitamins C and E did not protect against cancer

>  Alpha tocopherol, Vitamin C and beta carotene had no effect on cancer incidence or mortality

>  Vitamins A, C and E with beta carotene alone or in combination did not prevent gastrointestinal cancers

>  Alpha tocopherol and selenium failed to prevent prostate cancer in average risk men

In some instances studies actually showed an increased risk of cancer in those taking supplements.

Two different randomized trials showed an increased risk of cancer (prostate) and pre cancerous lesions (colonic adenomas) in individuals taking long term folic acid supplementation.

The paper was equally negative about Vitamin D use. They cited three short term studies that failed to demonstrate an effect of Vitamin D on cancer incidence or mortality. The authors went on to support the Institute of Medicine position that “there is not enough evidence to state that there is a causal association between low Vitamin D intake and increased cancer risk.”

The material was published in the Journal of the National Cancer Institute and summarized recently in the on line news service MedPage.

In my practice I will continue to emphasize that a balanced diet prepared in a manner to preserve the nutrients is the best way to meet your nutritional needs. I will screen for those malabsorptive states and surgical situations that require supplementation with vitamins and supplements. These are sufficiently rare. In some cases, administration of medications such as anti-cancer agents causes depletion or malabsorption of vitamins and trace elements. In those cases I will supplement.  Women requiring calcium to prevent osteopenia and osteoporosis should be supplemented. In most other instances, I will suggest a balanced diet and correct preparation of food which should provide all the vitamins, minerals and antioxidants needed to stay healthy