Introduction After menopause, the levels of sex hormones decline, and women often develop postmenopausal
osteoporosis. Since steroid hormone therapy has negative side effects, use of non-steroidal
selective androgen and estrogen receptor modulators (SARMs or SERMs) could be a possible
treatment option. Raloxifene (RAL), a SERM is approved for treatment of postmenopausal
osteoporosis. Ostarine (OS), a SARM has been shown to improve bone parameters in ovariectomized
rats. The present study analyzes the effect of OS and RAL applied as a combination
therapy or alone on bone properties in an ovariectomized rat model of postmenopausal
osteoporosis.
Methods Three-month old female Sprague-Dawley rats were either left intact (Non-Ovx, n = 15)
or were ovariectomized (Ovx, n = 75). Ovx rats were divided into 4 groups (n = 15
each): 1) no treatment (Ovx), 2) OS treatment (Ovx + OS), 3) RAL treatment (Ovx + RAL),
4) OS + RAL treatment (Ovx + OS + RAL). OS and RAL were administered to the rats along
with a soy-free diet for up to 13 weeks. The average daily doses were 0.6 mg/kg body
weight (BW) for OS and 11 mg/kg BW for RAL. The lumbar vertebral bodies and femora
were examined by micro-CT, biomechanical and ashing analyses. The weights of whole
body, visceral fat and uterus were recorded. Serum alkaline phosphatase (Alp) and
collagen type 1 cross-linked C-telopeptide (Ctx) were measured. Statistical analysis
was performed using one-way ANOVA and Tukey-test (p < 0.05).
Results RAL treatment alone increased cortical and trabecular density, trabecular area and
total bone density. OS alone enhanced number of trabecular nodes and trabecular area.
Combined OS + RAL treatment improved most of the cortical and trabecular structural
parameters and biomechanical properties. In serum, Ctx was lower, and Alp was higher
in OS + RAL compared to Ovx. Uterus weight was the lowest in Ovx and Ovx + RAL groups,
whereas OS and OS + RAL treatments increased it to the weight in the Non-Ovx group.
BW and muscle weight were increased by OS treatment while RAL and RAL + OS maintained
them at the level of Non-Ovx rats. Visceral fat weight was reduced after all three
treatments.
Discussion RAL and OS possessed distinct effect patterns on the different organ systems. The
combination therapy RAL + OS showed stronger effects on bone tissue than single therapies
and could be a therapeutic option in the treatment of postmenopausal osteoporosis.
However, side effects of OS therapy on the reproductive tissue should be considered.
Keywords selective androgen receptor modulator, selective estrogen receptor modulator, bone,
ovariectomized rat model, postmenopausal osteoporosis
Korrespondenzadresse Komrakova Marina, Universitätsmedizin Göttingen, Klinik für Unfallchirurgie, Orthopädie
und Plastische Chirurgie, Robert-Koch Str. 40, 37075 Goettngen, Deutschland, Germany
E-Mail komrakova@yahoo.com
