Histological techniques, by enabling direct observation of the tissues, yield highly accurate data on the effects of a product on bone. We compared the effects of long-term daily treatment with Femarelle^® (DT56a), E₂, and placebo on the skeletal histology of ovariectomized (OVX) and non-OVX rats in order to study the dynamics of their effects on the rebuilding process in different parts of the bone.

Thirty rats were divided into four groups. Rats in the control group were left with intact ovaries and those in the other groups underwent ovariectomy. The OVX rats were treated for 2 months with Femarelle^®, E₂, or placebo (control). Histomorphometry of the trabecular bone volume (TBV) in each rat (expressed as a percentage of the total bone volume), as well as cortical thickness and growth plate width, were recorded by a computerized system. In addition, Creatine Kinase (CK) specific activity, a marker of estrogen receptor activation, was analyzed in the skeletal tissues and in the uterus.

Results

The OVX rats showed substantial losses of TBV, cortical thickness and growth plate width, with the result that they were markedly osteoporotic relative to non-OVX rats.

Sample histology slides showing the effects of treatment with Femarelle^®, E₂ and a vehicle on bone

Treatment with Femarelle^® and with E₂ prevented the bone loss following OVX, maintaining all parameters to non-OVX control levels.

A significant increase in CK activity was found following E₂ and Femarelle^® treatment in the skeletal tissues (Epiphysis and Diaphysis). However, while E₂ produced significant CK activation in the uterus, Femarelle^® had no stimulatory effect in that site.

Conclusion

Since peak bone mass in women is reached around the age of 28, comparing the bone structure of a young rat to that of an OVX one following treatment with Femarelle^® provides the best indication regarding the properties of Femarelle^® on bone build-up and bone health preservation.

This study serves as further proof of the beneficial effect of Femarelle^® on the bone without affecting the uterus.

Publication

British J. of Obstetrics & Gynecology 2005; 112(7):981-985: “DT56a (Femarelle/Tofupill) Stimulates Bone Formation in Female Rats”; Somjen, D., Yoles, I. et al