Teriparatide BMD results after other therapies
Teriparatide (Forteo) daily injections have been shown in many studies to be highly effective stimulators of bone formation which then reduces fracture rates in people with osteoporosis. Many people who start taking Forteo have been taking other approved forms of therapy for osteoporosis, such as bisphosphonates or HRT for women. It hasn't been known if this pretreatment with other osteoporosis medications has any effect on the efficacy of Forteo to treat osteoporosis. The recent study done on ovariectomized rats by May YL and others, PMID: 12697709, found no negative effects from the pretreatment. An interesting side finding was that the rats treated with alendronate (Fosamax) showed mechanically improved bone compared to the rats pretreated with estrogen or raloxifene. The authors attributed this to the combined building of new bone trabeculae along with the prevention of breakdown of the old trabeculae when alendronate was used. The authors found that, "Teriparatide enhanced mineralizing surface, mineral apposition rate, and bone formation rate in all groups." Bone strength and toughness improvement was similar in all groups compared with 10 month levels. Thus, there would appear to be no deleterious effect from pretreatment with other approved osteoporosis medications when starting Forteo. Editor's note: It would be interesting to see this same study repeated with alendronate being taken throughout the ten-month trial to see if there is an increased benefit from taking Forteo with a bisphosphonate. That appears to be a distinct possibility, with little chance of decreased benefit from the combined medications.
Genetic makeup and alendronate effectiveness
Study results are always reported as "mean increase or decrease" in bone mineral density (BMD) after taking some medication. So this means the average result for those in the study group will show improvement or lack thereof. That doesn't mean that some people in the study group don't have results that are considerably different from the mean result. In fact, I have reported that in Updates on this Website where two people in the Forteo group and three in the alendronate group of a study actually lost BMD while the mean increase of the group was from 3 to 5%, or more. It would be interesting to know why some people don't respond so improved therapies could be designed for them. It is possible that genetic makeup could be one cause of this type of problem. A recent study by Palomba S and others, PMID: 12608943, found differences in the effectiveness of alendronate based upon the Bsml vitamin D receptor (VDR) genotypes of the participants. This is a complex topic that I'll try to summarize for readers, but I can't promise anything. The genotype is the actual gene type or code, in this case the one that governs the use of vitamin D by the body. There are three possible genetic codes: BB, Bb, or bb that could make up this genotype. Women were typed according to their vitamin D receptor gene code before the study started. Basically, the authors found the bb genotype responded better to treatment than BB genotype, but not significantly better than the Bb genotype. The bb genotype is the predominate VDR receptor code, with Bb and then BB next in prominence. Thus, the BB genotype individuals are a relatively small proportion of the population, and this could help explain the small numbers of individuals who don't appear to respond normally to accepted osteoporosis therapies. Editor's note: So, if you are a non-responder to accepted osteoporosis therapy, you might ask for a determination of your VDR genotype. I'm not sure that would enable you to find a therapy that works, but at least you would know why you aren't responding.