Osteoporosis & Paget’s Disease

• Osteocytes or bone cells that maintain bone as living tissue
• Osteoclasts or bone breakers that destroy bone
• Osteoblasts or bone builders that form the supporting matrix of new bone

Osteoporosis or “holes in the bones” causes the bones to become brittle and is the leading bone disease in the United States. The progressive decrease in bone density occurs in both men and women, but is most common among postmenopausal women when bone resorption (destruction) exceeds that of bone formation. To maintain bone density, the body requires an adequate supply of calcium and other minerals and must produce the proper mix of several hormones as well as an adequate supply of vitamin D to absorb calcium from food. When the body is not able to regulate the mineral content of bones, they become less dense, more fragile and more prone to fracture. From age 50 to 90, the risk of hip fracture in white women (Caucasian and Asian women have a higher risk factor for osteoporosis) increases 50-fold and the risk of vertebral fracture increases 15- to 30-fold. It is estimated that 40 percent of 50-year-old women will sustain one or more osteoporo-sis- related fractures of the spine, hip, or wrist during their remaining lifetimes. Hip fractures in particular, are associated with substantial morbidity, disability, and mortality in both men and women over 70. There are 1.3 million osteo-related fractures in the U.S. each year. Osteoporosis has long been considered a woman’s disease – an estimated 23 million women have osteoporosis – so not many studies have been done with men. Studies focused on men are not far off. Presently it is estimated that 2 million men have osteoporosis with another 3 million at risk.

Paget’s Disease, named for Sir James Paget, an English doctor who first described the disease’s characteristics in 1876, is the second most common bone disease in the United States. Often pain-ful, Paget’s Disease is a disruption in the normal activity of bone tissue. Overly large osteoclasts dissolve bone too quickly – up to 50 times faster than normal. Osteoblasts try to compensate for the increased pace by hurriedly depositing new bone, but the rate is so rapid that the new bone is loose and bulky in structure, rather than strong, compact, and neatly arranged. Over time, the affected bone becomes weak and soft and can easily bend and may shorten the leg or spine. The disease can also enlarge the diameter of the bone. No bone is sacrosanct, but the most common bones affected are those of the spine, skull, pelvis, and legs. Deformities include bowed legs, an enlarged head or pelvis, and a curved back. If it changes bones around joints, it can cause arthritis or dental prob-lems when it affects facial bones. People with Paget’s and heart disease may be at greater risk for heart failure because Pagetic bones often contain more blood vessels than normal so the heart has to work harder to pump the extra blood required. It is estimated that three percent of the population over 40 is affected, but because it often develops without symptoms, 58 is the average age of diagnosis.

There is no known cause for Paget’s Disease, but genetics are strongly suspected because the disease tends to run in families. According to the Paget Foundation, the disease is most common in Cauca-sian people of Anglo-Saxon and European descent, but it also occurs in African Americans. It is rare in people of Asian descent. The precise gene has yet to be identified, but Frederick Singer, M.D., an endocrinologist at St. John’s Hospital (Santa Monica, CA), has traced an abnormality to chromo-some 18. Singer and other experts also suspect that a slow virus (one which does not cause symp-toms for many years) may play a role because osteoclasts from patients with Paget’s Disease contain the measles virus messenger RNA whereas osteoclasts of people without the disease do not contain this RNA.

Many people discover they have Paget’s purely by accident – from an x-ray taken for another reason or when a routine blood test shows an abnormally high level of total alkaline phosphatase, an en-zyme produced by osteoblasts as well as cells of the intestine and liver. When osteoblasts are overly active, the enzyme spills over into the blood. A normal serum alkaline phosphatase ranges from 20 to 141 units per liter. People with severe Paget’s Disease may have six to 10 times that range. One of the drugs prescribed to treat both osteoporosis and Paget’s Disease, is Fosamax™ (alendro-nate) which was approved by the FDA in 1995. Fosamax was approved for women only although the manufacturer, Merck, is sponsoring studies on men and has applied for FDA approval. Fosamax is an aminobisphosphonate that acts as a specific inhibitor of bone destruction by osteoclasts. Sim-plistically, the drug tips the balance in favor of bone building osteoblasts so new bone is being made faster than old bone is being destroyed. A constant supply of the drug is necessary to maintain the upper hand. The recommended dosage for osteoporosis is 10 mg. per day and a month’s supply costs $50.00. Dosage for Paget’s Disease can be as high as 40 mg. per day at a cost of $126.00 per month.

Fosamax is difficult to absorb. Patients are instructed to take the drug on an empty stomach with a minimum of 8 ounces of water at least 30 minutes before breakfast. Most important, patients should not to lie down until after their first food of the day. The drug warnings include esophagitis, esophageal ulcers and esophageal erosions along with irritation of the upper gastrointestinal tract. In fact, Fosamax is number one on the FDA’s list of drugs suspected for causing adverse reactions. (The reports which are voluntary, totalled 174,905 in the past year. Fosamax accounted for 3.5% or 6,197 of the reports.) Additionally, patients should be instructed not to chew or suck on the tablet or take the drug at bedtime.

No human trials were done with pregnant or nursing women, but those done with rats indicate that extreme caution be exercised by the physician and patient when considering Fosamax. The doses used for the rat studies were higher than those recommended for humans, but protracted labor, maternal late pregnancy death, and fetal death were observed.

Other side effects reported by the investigators included abdominal pain, nausea, indigestion, constipation, diarrhea, gas, acid regurgitation, vomiting, difficulty swallowing, abdominal bloating, gastritis, musculoskeletal pain, and headache. Avoid the drug if possible.