Osteoporosis Center of Los Gatos
Osteoporosis Information

Human Parathyroid Hormone (PTH) for Treatment of
Osteoporosis Update

Donald C. Silcox, M.D.

It has now been well over a year since the FDA approved PTH therapy for the treatment of osteoporosis. The only preparation available currently is brand name Forteo, which is recombinant human parathyroid hormone (rhPTH). It is important to recognize that this is human parathyroid hormone. Recombinant refers to the method of building the parathyroid hormone from amino acids (obtained from breaking down the molecular structure of microorganisms). The resulting structure is identical to that of the active part of the human PTH hormone.

All of the existing treatments for osteoporosis, which include estrogen, selective estrogen and receptor modulators (Evista), bisphosphonates (Fosamax and Actonel) and calcitonin (Miacalcin) act by reducing loss of bone mineral. These are called antiresorptive agents. They do not build bone. By reducing loss of bone mineral, the result is that there is an increased mineralization (laying down of calcium and phosphate) in what is left of the basic bone structure, but there is no rebuilding the bone that is lost in osteoporosis. It is important to understand that osteoporosis refers to a total loss of bone compared to normal. This would be a loss of calcium and phosphate, but also loss of the supporting structure, which is a protein matrix.

PTH therapy results in new bone formation in that there is a laying down of protein matrix, and mineralization occurs not only in the previous existing matrix, but in the new structure that is formed. PTH increases bone turnover, and it increases formation of bone more than resorption. The results of this are documented by an increase of bone density as measured at the osteoporosis center(s), but also a decrease in fracture compared to other forms of treatment. There is a 65-69 percent reduction in the chance of a new fracture in a person with osteoporosis, and a 77-86 percent reduction in the chance of a recurrent fracture in a person with osteoporosis.

Continuous elevation of parathyroid hormone (PTH) levels occurs in humans due to abnormal secretion of this hormone from the parathyroid glands located in the neck. This is called hyperparathyroid disease. Loss of bone mass occurs with resulting osteoporosis. However, intermittent elevation of PTH that occurs in the daily injections of PTH, as prescribed in the use of Forteo, results in the bone building described above.

As a result of our experience in the last year and a half, we have developed better guidelines as to who needs PTH therapy. Please understand that this is still in evolution.

  1. Patients who lose bone mass on antiresorptive therapy are candidates for the use of PTH. The amount of loss of bone that is significant enough to indicate treatment change will be calculated based on the degree of loss of bone involved and the precision of the study instrument at the particular site where it was done.

  2. The second group of people are those who are on antiresorptive agents, but are unable to continue taking them due to side effects. The area where this is most problematic is in patients who are on Fosamax or Actonel, but develop gastrointestinal side effects. An additional group is those people who have gastrointestinal abnormalities, such as prominent GERD and dysmotility of the esophagus, especially with a stricture.

  3. The third group are those patients who have been using an antiresorptive regimen, but who have developed a fragility fracture. That would definitely indicate that the antiresorptive agent had failed its mission.

  4. The fourth group is those patients who are on therapy, but evolve into high risk category. This would include patients who have a number of risk factors and start taking medications that can induce osteoporosis. An example is a patient with asthma, requiring steroids. The problem with glucocorticoid-induced osteoporosis will be discussed in another update.

Information regarding the use of PTH along with other forms of antiresorptive treatment is still in early phases of the study. It does appear that PTH and estrogen taken together produce an additive effect. Certainly, estrogen does not interfere with the action of PTH. The same would appear to be true with the selective estrogen modulators (Evista).

The addition of calcitonin to PTH appears to not result in any significant beneficial effect.

Bisphosphonate therapy has been found to interfere with the action of PTH, and combination therapy is contraindicated based on this finding. The bisphosphonates, Fosamax and Actonel, have an extremely long presence in the bone after being discontinued (six months or more). There are studies emerging that show the effect of PTH on bone can be blunted for many months after discontinuing a bisphosphonate. Since PTH therapy is given only for two years, the open question is whether the increase in bone density at the end of the two years will be blunted in the patient that had been taking a bisphosphonate. Most importantly, would there be a decrease in fracture protection? Some physicians have suggested discontinuing the bisphosphonate months before starting PTH. There is no good data to determine if that period off the bisphosphonate would increase the risk of fracture. For now, it is best to start PTH immediately following cessation of Actonel or Fosamax.

The last indication for treatment is those patients who have osteoporosis and have not been on any pharmacological treatment. The situation where this would be a consideration would be a patient with osteoporosis who has had a fracture and who has had a marked loss of bone mass, perhaps in the neighborhood of 30-40 percent.

PTH is given for two years. At the end of that period, the increase in bone density and decrease in fracture risk is substantial. Once PTH has been stopped, there is a gradual decrease in bone density. One would assume that fracture protection would also decrease, but this has not been studied. Starting or restarting a bisphosphonate eliminates this falloff of bone density. Thus, it is necessary to start or resume a bisphosphonate following PTH treatment. This raises problems with those patients who could not take Fosamax or Actonel due to side effects. This issue will be discussed in the update section on Bisphosphonates .

There have now been well over 20,000 patients treated with PTH therapy since the drug has been approved. The side effects have been pretty much as predicted. Some patients develop muscle cramps, but in most cases this has been transient. There has been found to be a slight rise in serum calcium levels in the first few months, but this has not been significant and has not resulted in any complications. There have been no incidents of bone cancer that have occurred.

There is ongoing documentation, both with the manufacture of Forteo and with the FDA, for any adverse occurrences with PTH.

In summary, the experiences that we have had with PTH therapy during this initial period of time have been extremely rewarding, with the result of significant reduction in fractures in people with osteoporosis.

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