En excerpt from the book :
IN CANCER THERAPY"
by Ross, R.Ph. Pelton, Lee Overholser
THE GOOD NEWS is that there is finally an effective treatment for bone cancer—a drug named clodronate. The bad news is that clodronate is not directly available in the United States.
Few diseases are as dehumanizing and as damaging to a person's quality of life as bone cancer. The disease causes a loss of calcium from the bones, making the slightest movement exhausting and painful. The pain often becomes unmanageable, even with the strongest pain medication. The loss of calcium from the bones usually leads to hypercalcemia (an excess of calcium in the bloodstream), which can result in kidney failure. The bones become so brittle that a cough or an abrupt movement can cause bone fractures, and these are very slow to heal.
Clodronate prevents hypercalcemia and normalizes the level of calcium in the bloodstream. It also stops or reduces the spread, or metastasis, of the cancer to new sites and can retard, arrest, and even reverse the growth of existing metastases. In addition, this drug greatly reduces the risk of fractures and is very effective at alleviating bone pain.
Many people think of bones as inert, rigid structures. In reality, bone is a living tissue. Throughout life the mineral salts in the skeleton are involved in a continual process of being dissolved (called resorption) and reformed. These minerals, especially calcium, are circulated throughout the body to be used in hundreds of activities, ranging from muscle contraction to the transmission of nerve impulses. The bones act like banks that store and distribute minerals for the body.
Two types of cells, the osteoblasts and the osteoclasts, regulate bone resorption and reformation. The osteoblasts aid in depositing calcium and other minerals in the bones, while the osteoclasts cause old bone to dissolve and release minerals into the bloodstream, raising the serum levels of mineral salts. (8) When this process is proceeding normally, the phases of bone resorption and reformation are in balance.
Hypercalcemia Due to Malignancy
With bone cancer, the cycle of bone resorption and reformation is upset, due to the stimulation of bone resorption. The bones are eaten away, causing a buildup of calcium in the blood. When serum calcium levels rise, patients quickly become dehydrated;
the result is mental confusion, vomiting, and kidney failure. If the condition is left uncontrolled, cardiac dysrhythmia and death follow.
The ongoing process of bone remodeling is a balance between osteoclast-activated bone resorption and the osteoblast-activated formation of new bone. The key to the destruction of bone by bone cancer is the osteoclast. Tumor cells in the bone cause the release of substances that in turn cause an increase in the size, number, and activity of osteoclasts. (3) The cancer-induced activation of the osteoclasts upsets the normal balance, causing increased degradation of the bone and an increase in bloodstream or serum calcium levels.
The Bone Cancer Answer
Clodronate may be the bone cancer answer. I have supervised the therapy for hundreds of patients with bone cancer over the past four years. In my opinion, clodronate is the most effective therapy for bone cancer that is available today. Clodronate facilitates recalcification and remineralization of the areas of bone affected by cancer. Over time, many of my patients taking clodronate have ended up with a "clean" bone scan.
Clodronate is a member of a group of chemicals called the bis-phosphonates, which are structurally similar to a substance called pyrophosphate that occurs naturally in the bones and in body fluids such as plasma, urine, and saliva. Pyrophosphates regulate the calcium balance, influencing the processes of the resorption of old bone and the building of new bone.
The pyrophosphate molecule is characterized by a link between two phosphate atoms and a single oxygen atom, forming a bond that chemists write in the form P-O-P. The bisphos-phonates substitute a carbon atom for the oxygen, to form a P-C-P bond, which can accept side chains on the carbon atom. Slight changes in the side chains attached to the carbon atom lead to extensive changes in the biological and therapeutic properties of bisphosphonates.
Due to their structural similarity to pyrophosphates, the bisphosphonates are able to regulate calcium balance in the body. (7) To date, clodronate, with its two chlorine atoms attached to the carbon atom, has the strongest known biological activity of any known bisphosphonate.
The Effect of Clodronate
Clodronate binds to calcium, which gives it a strong affinity to bone. This enables it to stop the osteoclastic activity of bone resorption. Thus, administration of clodronate results in a prompt suppression of increased bone resorption and a return to normal bone turnover. (11)
Radiation and chemotherapy are marginal at best in the treat-ment of bone cancer. Their side effects and limitations are well known and documented. Radiation can be effective in reducing the pain of bone cancer, but it does not stop the progression of the disease. Where bone cancer is concerned, radiation and chemotherapy can be viewed only as palliative types of therapy.
Clodronate, however, is able to effect sustainable improvements in the underlying problems associated with bone cancer. The efficacy of clodronate in the treatment of metastatic bone cancer has been documented in numerous studies.
To date, nearly thirty clinical studies have documented clodron-ate's effectiveness in reducing cancer-induced hypercalcemia. In one representative study, twenty-seven patients with malignant hypercalcemia were treated with intravenous clodronate. Serum calcium levels decreased significantly in two days, and 89 percent (twenty-four patients) reached normal calcium levels within four days. (16)
Other drugs, such as calcitonin, mithramycin, glucocorticoids, and prostaglandin synthetase inhibitors, are used to treat elevated calcium levels due to malignancy. However, these approaches are less effective than clodronate, and they have greater side effects. The efficacy and low toxicity of clodronate clearly makes it the drug of choice in countries where it is available.
In a placebo-controlled study, oral clodronate was administered to patients for twelve months. Urinary calcium, hydroxy-proline (HOP), and serum calcium all normalized. Most significant was the fact that 88 percent of the clodronate-treated patients experienced a reduction in pain, versus only 18 percent on placebo. (4)
In a double-blind study oral clodronate was given to patients for six to eighteen months. The clodronate-treated patients showed a signi