A recent NEJM (New England Journal of Medicine) article by Dennis Black MD denying a link between Fosamax and spontaneous mid-femur fractures has many doctors raising their eyebrows. Firstly, there is the problem of conflict of interest. The study was funded by Fosamax maker, Merck, and the authors are all on Merck’s payroll.
Secondly, a number of flaws in the study are brought out by Dr Elizabeth Shane who says in a NEJM Editorial: No Xray data was presented, although every patient with a fracture had xrays. The women were on Fosamax for shorter time and lower dosage required to generate the femur fractures. The statistics of the study was questioned. In spite of Dr Black’s reassuring report, Dr Elizabeth Shane still recommends a drug holiday. This is a polite way of saying, “STOP THE DRUG”. Dr Shane says: “it is reasonable to consider drug holidays.”
I have a few more questions and comments about Dr Black’s NEJM report.
1) The patient data was not stratified according to T score. The FIT trial showed increased fracture rates in patients on Fosamax with T scores greater than -2.5. Fosamax doubled the hip fracture rate in this group (T score above -2.5) from 6 to 11.
2) Although there were 284 hip fractures, 135 were excluded from the data for various reasons, and only 12 were accepted as spontaneous mid-femur fractures. Whenever data is excluded from a data set, this arouses suspicion and a red flag of possible data manipulation.
Another question: since there was no Xray data, how can the fractures be reviewed and excluded without this? If there was Xray review, then why wasn’t this data included in the study?
3) Why do the results of Dr Dennis Black contrast with the many reported case series on Fosamax induced spontaneous femur fractures from Joseph Lane, Odvina and Goh (and many others).
Dr Black’s results run counter to the experience of the medical community. Physicans are seeing and reporting more cases of atypical femur fractures on Fosamax. We never saw these before the Fosamax era.
4) Why do the results of Dr Dennis Black contrast with bone histology studies that show abnormal bone formation on Fosamax, reporting “microdamage accumulation and reduced some mechanical properties of bone”.
5) Why are these spontaneous mid-femur fractures happening at all? Doesn’t this indicate a severe problem with the underlying bone physiology? The bisphosphonate drug is producing abnormal, pathological bone demonstrated on histology slides. Dr Black’s report does not address this question.
6) What about reports of a link with Osteonecrosis of the Jaw, another example of Fosamax disturbing bone physiology, making the bones weaker, not stronger. Dr Black’s report does not address this issue.
Dr. Black reports to the NEJM that he is receiving grants (to UCSF) from Merck, Novartis, Amgen, and Roche and travel reimbursements from Merck and Novartis, who also supported the research. The study was sponsored by Merck and Novartis. Several other authors work for the companies, while others consult and receive compensation for their work from the makers of bisphosphonates.
Bottom line: Dr Black’s report is unconvincing. Especially unconvinced are the increasing numbers of women presenting to the orthopaedic surgeons with spontaneous femur fractures on Fosamax. These fractures are devastating and do not heal.
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