Atorvastatin, a double weapon in osteoporosis treatment: an experimental and clinical study

Abstract

ObjectiveThe aim of this study was to evaluate the effect of atorvastatin on the bone formation and resorption markers in ovariectomized rats (experimental study), and to study its effect on the bone mineral density (BMD) in postmenopausal osteoporotic women (clinical study).Materials and methodsThe study involved experimental and clinical aspects. In the experimental aspect, 42 female Wistar rats were divided into five groups: Group I (n=6; sham-operated), Group II (n=6; 1 mL of carboxymethyl cellulose [CMC] was administered orally), Group III (n=6; 20 mg/kg orally of atorvastatin was administered), Group IV (n=12; untreated ovariectomized [OVX] rats and served as a model of osteoporosis [OP]) and Group V (n=12; 20 mg/kg orally of atorvastatin was administered to ovariectomized rats). After 4 weeks, serum acid phosphatase, alkaline phosphatase, osteocalcin, total calcium and inorganic phosphorus were assessed. Then, 3 µm thickness lumbar and femur sections were examined using a light microscope to assess cortical thickness, trabecular area, numbers of osteoblasts and osteoclasts. In the clinical aspect, 85 post-menopausal osteoporotic females with recently detected hyperlipidemia participated in the study. Atorvastatin 40 mg/day, calcium carbonate 500 mg/day and vitamin D 800 international units were given to all patients for a period of 18 months. BMD was measured at the start and at the end of the study by dual-energy X-ray absorptiometry (DEXA).ResultsIn the experiment aspect, the biomarkers of bone remodeling were notably elevated in the OVX group. Administration of atorvastatin produced a significant decrease in the level of these bone metabolic markers. Atorvastatin significantly ameliorates osteoporotic changes induced by ovariectomy. In the clinical aspect, after 18 months the DEXA showed improvement in the T-score for the three measured zones; however, these changes were statistically significant only in the femoral neck area.ConclusionAtorvastatin was able to decrease the rate of bone metabolism and increase osteogenic activity. It has dual mode of action; both anabolic and antiresorptive effect on bone. This lipophilic statin member may act as a double weapon drug.

27-Hydroxycholesterol, an endogenous selective estrogen receptor modulator

“…Interestingly, several studies have now indicated that post-menopausal women taking cholesterol lowering drugs such as statins (HMGCoA reductase inhibitors) have better bone health [42, 43]. Furthermore, elevated cholesterol is a recognized risk factor for osteoporosis in post-menopausal women [44–48].…”

Saururus chinensis Prevents Estrogen Deficiency-Induced Osteoporosis in Rats: A Metabolomic Study Using UPLC/Q-TOF MS

“…Moreover, the levels of biochemical markers, including osteocalcin (OC), alkaline phosphatase (ALP), and deoxypyridinoline (DPD), in the OVX group were significantly higher than those in the sham group. In OVX group, serum ALP levels, which are a bone turnover marker, and OC levels, which are a bone formation marker, were significantly elevated [30]. The body weight, as well as OC, ALP, and DPD levels, significantly decreased in the SCE-treated group compared with those in the OVX group.…”

In Situ Self‐Assembling Micellar Depots that Can Actively Trap and Passively Release NO with Long‐Lasting Activity to Reverse Osteoporosis

“…The levels of serum biomarkers of ALP and osteocalcin in the OVX rats that received PBS or free NONOate were significantly higher than those in the healthy control rats (Figure e, P < 0.05), owing to compensation for increased bone turnover . However, the OVX‐induced increases in ALP and osteocalcin were significantly suppressed by treatment with MPs ( P < 0.05).…”