Glossary
Supportive Therapies
Bisphosphonates
Zometa is one of a class of medications that come in oral and intravenous forms call bisphosphonates. Bisphosphonates can be used to treat osteoporosis or metastatic cancer in the bones. The oral bisphosphonates, Fosamax, Boniva and Actonel are primarily for osteoporosis. The intravenous bisphosphonates, Zometa and Aredia, are primarily for cancer, though they are also potent anti-osteoporosis agents.
Mode of Action
Normal bone is metabolically active. The bone matrix is constantly being remodeled and bone density is the net effect of two very active processes, the rate of bone breakdown affected by the osteoclasts and the formation of new bone by the osteoblasts. Weakening of the bones through calcium loss - osteoporosis - occurs when the formation of new bone lags behind the rate of bone breakdown. Bisphosphonates counteract osteoporosis by slowing the rate of bone breakdown and allowing the osteoblasts to "catch up". In regards to the anticancer effect of bisphosphonates, by inhibiting bone breakdown, growth factors in the bone matrix are kept "locked up," out of reach to the cancer cells. Without access to these growth factors, cancer cell growth is inhibited.
Osteoporosis
Calcium loss from the bone is a silent phenomenon until a fracture occurs. Common fracture sites from osteoporosis are the spine, rib, wrist and hip. Bone fractures result in higher mortality in men with prostate cancer. Compression fractures of the spine can be extremely painful and lead to a loss in height. Advanced osteoporosis causes an ugly forward curvature of the spine commonly termed the "dowagers hump."
A common misperception is that osteoporosis occurs mainly in females. But one-third of all hip fractures in the United States occur in men. There are many causes. Slender men have less bone reserve and are more predisposed. Thyroid or parathyroid hyperactivity, excessive alcohol, caffeine or tobacco all contribute. Cortisone, used to treat asthma or arthritis, is another common culprit. Lack of exercise, lack of sunlight (low vitamin D), and low calcium intake are additional potential causes.
Osteoporosis-induced bone fractures are even more frequent in men treated for prostate cancer with Testosterone Inactivating Pharmaceuticals (TIP). Loss of testosterone and the estrogen (that is derived from testosterone) accelerates calcium loss from bone.
Method of Administration
Oral bisphosphonates need to be administered on an empty stomach or the medicine won't be absorbed into the bloodstream. The most common side effect of the oral agents is heartburn. To minimize esophageal irritation incurred by drug reflux, the manufacturer recommends staying erect for an hour after taking the drug.
The advantage of the intravenous agents of Zometa or Aredia is that they bypass the stomach, avoiding concerns about stomach irritation. Also, 100% of the drug is guaranteed to get into the bloodstream. Their most common side effect is muscle soreness lasting a day or so. The soreness does not usually recur on subsequent infusions. The risk of muscle soreness can be reduced by giving intravenous decadron, a type of cortisone, just prior to the infusion.
For osteoporosis, Zometa or Aredia is given every three months. For the treatment of cancer in the bones, the recommended frequency of infusions is monthly.
Osteonecrosis
Osteonecrosis of the jaw is a bone spur breaking through the skin of the gums leaving exposed bone. When the bone gets infected, it can be quite painful. Antibiotics give relief but pain returns when they are stopped. When osteonecrosis was first reported, the connection with bisphosphonates was not immediately recognized. In many patients the treatment was unknowingly continued. This led to the discouraging conclusion that the osteonecrosis was irreversible and untreatable. We now know that osteonecrosis resolves after the bisphosphonates are stopped.
Osteonecrosis is usually triggered by an ill-advised tooth extraction. Men on bisphosphonates should never have a tooth pulled without first discussing the situation with their doctor. Other forms of dental work such as cleaning, fillings and root canals are not a concern.
Xgeva
Xgeva was FDA approved in 2010 as an injectable medication with many properties similar to bisphosphonates like Zometa. One study comparing Xgeva directly with Zometa showed a lower incidence of skeletal related events. Overall, risks and benefits are similar to Zometa.
Samarium & Strontium
Prostate cancer in the bones accelerates bone remodeling which increased calcium uptake. Because the samarium and strontium are similar to calcium in their chemical makeup, injected radioactive samarium or strontium concentrates near the cancer. Improvement of bone pain is commonly seen. In some studies, there is a trend to improved survival. Unfortunately, like other forms of radiation both samarium and strontium tend to cause collateral damage to the bone marrow with suppression of blood counts.
Neulasta & Aranesp
White blood cells, the first line of defense against infection, are often transiently suppressed with chemotherapy. Neulasta is a powerful medicine that stimulates the bone marrow to manufacture white blood cells more quickly and in greater numbers. Side effects are rare but occasionally serious but transient episodes of lower back pain can occur.
Anemia is a common side effect of hormone therapy, chemotherapy, and from progressive prostate cancer. Sometimes blood transfusions are required to offset the low red blood cell count. Anemia can be associate shortness of breath and fatigue. Aranesp is an injectable medication that stimulates the bone marrow to make more red blood cells. Timely and appropriate use of Aranesp can help maintain normal red blood cell counts and help avoid the need for blood transfusions.
