Raloxifene and vitamin K2 combine to improve the femoral neck strength of ovariectomized rats.
We evaluated the skeletal effects of two osteoporosis therapies in an ovariectomized rat model, raloxifene and vitamin K2, as well as the vitamin K2 plus raloxifene (K + Ral) combination. In two studies, 6-month-old rats were ovariectomized, except for sham-ovariectomy controls (Sham), and dosed orally with vehicle, 30 mg/kg vitamin K2, 1 mg/kg raloxifene, or the combination of K + Ral for 6 weeks following surgery. Vitamin K2 had no effect on serum estrogen, low-density lipoprotein cholesterol (LDL-C), or urinary deoxypyridinoline levels, but slightly increased osteocalcin levels compared to Ovx. Raloxifene lowered total cholesterol, LDL-C, osteocalcin, and urinary deoxypyridinoline levels to below Ovx levels, while having no effect on estrogen levels. Raloxifene, but not vitamin K2, prevented ovariectomy-induced loss of bone in the distal femoral metaphysis and proximal tibial metaphysis, as did the K + Ral combination.Raloxifene, but not vitamin K2, partially prevented, loss of vertebral bone mineral density (BMD), whereas K + Ral had BMD greater than that of Ovx. Vitamin K2 increased bone formation rate to above Ovx, whereas raloxifene and K + Ral reduced bone formation rate to Sham levels. Vitamin K2 had no effect on eroded surface compared to Ovx, while raloxifene and K + Ral reduced eroded surface to Sham levels. Groups were not different in the BMD of femoral midshaft; however vitamin K2 was observed to increase periosteal mineralizing surface of the tibial shaft to above Ovx, while raloxifene reduced periosteal mineralizing surface toward Sham levels. Femoral neck strength was not different between groups, indicating no significant beneficial effect of either raloxifene or vitamin K2 at this site. However, K + Ral had reproducibly greater femoral neck strength than Ovx or Sham. Raloxifene, but not vitamin K2, partially prevented loss of lumbar vertebra strength; but K + Ral was not different from Sham or Ovx. Therefore, raloxifene and vitamin K2 had complementary effects on bone resorption and formation activities, respectively, resulting in a reproducible, significant improvement of femoral neck strength. These rat data suggest interesting therapeutic possibilities that may require clinical verification.
Iwamoto J, Yeh JK, Schmidt A, Rowley E…
Calcif. Tissue Int. Aug 2005 PMID: 16059775
Comparative effects of risedronate, atorvastatin, estrogen and SERMs on bone mass and strength in ovariectomized rats.
The aim of this study was to investigate bone protective effects of risedronate, atorvastatin, raloxifene and clomiphene citrate in ovariectomized rats.
Our study was conducted on 63 rats at Experimental Research Center of Celal Bayar University. Six-month-old rats were divided into seven groups. There were five drug administered ovariectomized groups, one ovariectomized control group without drug administration and one non-ovariectomized control group without drug administration. Eight weeks postovariectomy, rats were treated with the bisphosphonate risedronate sodium, the statin atorvastatin, the estrogen 17beta-estradiol and the selective estrogen receptor modulators (SERMs) raloxifene hydrochloride and clomiphene citrate by gavage daily for 8 weeks. At the end of the study, rats were killed under anesthesia. For densitometric evaluation, left femurs and tibiae were removed. Left femurs were also used to measure bone volume. Right femurs were used for three-point bending test. Compared to ovariectomized group, femur cortex volume increased significantly in non-ovariectomized group (p=0.016). Compared to non-ovariectomized group, distal femoral metaphyseal and femur midshaft bone mineral density values were significantly lower in ovariectomized group (p=0.047). In ovariectomy+atorvastatin group, whole femur and femur midshaft bone mineral density and three-point bending test maximal load values were significantly higher than ovariectomized group (p=0.049, 0.05, and 0.018). When compared to the ovariectomized group, no significant difference was found with respect to femoral maximum load values in groups treated with risedronate, estrogen, raloxifene and clomiphene (p=0.602, 0.602, 0.75, and 0.927). In ovariectomy+risedronate group, femur midshaft bone mineral density values were significantly higher than the values in ovariectomized group (p=0.023). When compared to ovariectomized group, no significant difference was found with respect to femur midshaft bone mineral density values in groups treated with estrogen, raloxifene and clomiphene (p=0.306, 0.808, and 0.095).
While risedronate sodium prevented the decrease in bone mineral density in ovariectomized rats, atorvastatin maintained mechanical characteristics of bone and also prevented the decrease in bone mineral density as risedronate sodium.
Uyar Y, Baytur Y, Inceboz U, Demir BC…
Maturitas Jul 2009 PMID: 19386450
Here is a nice talk by Dr. Heather Hofflich from May 15, 2013. She’s an Associate Professor of Medicine at UCSD. She gives an overview of osteoporosis and discusses the causes and therapies used to treat it. She also takes a look at recent controversies in treatment plans and vitamin usage.
One thing that bothers me about her talk is that she claims Teriparatide is the only thing in the world that builds bone by increasing osteoblast activity. I’ve posted many studies that found increases in osteoblasts from a variety of things. She also didn’t mention any other potentially helpful dietary supplements besides Calcium and Vitamin D. Like most MDs, she is probably unaware of anything that is not FDA approved.
Hydrolyzed collagen improves bone status and prevents bone loss in ovariectomized C3H/HeN mice.
This study evaluates the effect of hydrolyzed collagen (HC) on bone health of ovariectomized mice (OVX) at different ages. Twenty-six weeks after the OVX procedure, HC ingestion was still able to improve significantly bone mineral density (BMD) and some femur biomechanical parameters. Moreover, HC ingestion for 1 month before surgery prevented BMD decrease.
HC can play an important role in preserving BMD before osteoporosis appears. The aim of this study was to evaluate the effect of HC on bone health of ovariectomized mice at different ages.
Female C3H mice were either OVX at 3 or 6 months and fed for 6 months (first experiment) or 3 months (second experiment) with diet including 0, 10, or 25 g/kg of HC. In the second experiment, one group received HC 1 month before surgery, and two groups received the supplementation immediately after surgery, one fed ad libitum and the other by gavage. Mice treated with raloxifene were used as a positive control. BMD, femur intrinsic and extrinsic biomechanical properties, and type I collagen C-terminal telopeptide were measured after 12 and 26 weeks. Food intake and spontaneous physical activity were also recorded.
The OVX procedure increased body weight, while food intake decreased, thus suggesting that resting metabolism was decreased. Ingestion of 25 g/kg of HC for 3 or 6 months reduced bone loss significantly in, respectively, 3- and 6-month-old OVX mice. The lowest HC concentration was less efficient. HC ingestion for 3 months is as efficient as raloxifene to protect 3-month-old OVX mice from bone loss. Our results also demonstrated that HC ingestion before surgery prevented the BMD decreases.
This study confirms that dietary collagen reduces bone loss in OVX mice by increasing the diameter of the cortical areas of femurs and can have a preventive effect.
Guillerminet F, Fabien-Soulé V, Even PC, Tomé D…
Osteoporos Int Jul 2012 PMID: 21927918
Effect of Cissus quadrangularis Linn on the development of osteopenia induced by ovariectomy in rats.
The aim of our study was to see the efficacy of petroleum ether extract of Cissus quadrangularis (CQ) on development of osteopenia in ovariectomy induced Wistar rats.
The female Wistar rats were ovariectomized or Sham operated. The rats were anesthetized with pentobarbital sodium (40 mg/ kg b.w, i.p.), the ovaries were removed bilaterally. Sham-operation was performed in the same manner but only exposing the ovaries (sham operated (SHAM) group). A day later, the ovariectomized rats were randomly divided into four groups of eight animals each. The groups are 1. Sham operated (SHAM), 2. Ovariectomized (OVX), 3. Ovariectomized and treated with 25 mg/kg b.w of raloxifene (OVX+RAL), 4. Ovariectomized and treated with 500 mg/kg b.w of petroleum ether extract of CQ (OVX+CQ). The treatment continued for 30 days. At the end of the treatment, rats in all groups were sacrificed by cervical dislocation. Before sacrifice, blood was collected for the estimation of serum ALP, TRAP, Calcium and hydroxyproline; where as the left femur was used for histomorphometrical analysis.
The findings assessed on the basis of animal weight, morphology of femur, histomorphometry and biochemical analysis. As compared to SHAM group, OVX group animals showed a significant rise in serum ALP, TRAP and hydroxyproline levels at the end of 1 month following ovariectomy while no significant change was seen in the serum calcium levels. ALP and TRAP levels of OVX + RAL and OVX + CQ groups showed a further increase following administration of raloxifene and Cissus quadrangularis. The serum hydroxyproline content was found to be increased in the OVX + CQ compared to SHAM group. CQ significantly increased the thickness of both cortical (p <0.001) and trabecular bone (p <0.001).This action of CQ is comparable to action of Raloxifene. These data suggest a strong anti-osteoporotic activity of CQ.
The results confirm, at least in part, for the use of Cissus quadrangularis in folk medicine to treat osteoporosis.