Unfavorable effects of memantine on the skeletal system in female rats.

Memantine is an N-methyl-D-aspartate (NMDA) receptor antagonist used in the treatment of Alzheimer's disease (AD). NMDA receptors are expressed on bone cells. The aim of the present study was to investigate the effects of memantine on the rat musculoskeletal system. Taking into account that most of female AD patients are postmenopausal, the study was carried out on intact and ovariectomized (estrogen-deficient) rats. Mature Wistar rats were divided into following groups: non-ovariectomized (NOVX) control rats, NOVX rats treated with memantine, ovariectomized (OVX) control rats, and OVX rats treated with memantine. Memantine (2 mg/kg p.o.) was administered once daily for four weeks, starting one week after ovariectomy. The serum bone turnover marker and cytokine levels, bone density, mass, mineralization, mechanical properties, histomorphometric parameters of compact and cancellous bone, skeletal muscle mass and grip strength were determined. In NOVX rats, memantine slightly decreased the strength of compact bone of the femoral diaphysis (parameters in the yield point) and unfavorably affected histomorphometric parameters of cancellous bone (the femoral epiphysis and metaphysis). In OVX rats, in which estrogen deficiency induced osteoporotic changes, memantine increased the phosphorus content in the femoral bone mineral. No other effects on bone were observed in the memantine-treated OVX rats. In conclusion, the results of the present study indicated slight damaging skeletal effects of memantine in rats with normal estrogen levels.

Effects of Donepezil on the Musculoskeletal System in Female Rats.

The extension of human life makes it more and more important to prevent and treat diseases of the elderly, including Alzheimer's disease (AD) and osteoporosis. Little is known about the effects of drugs used in the treatment of AD on the musculoskeletal system. The aim of the present study was to investigate the effects of donepezil, an acetylcholinesterase inhibitor, on the musculoskeletal system in rats with normal and reduced estrogen levels. The study was carried out on four groups of mature female rats: non-ovariectomized (NOVX) control rats, NOVX rats treated with donepezil, ovariectomized (OVX) control rats and OVX rats treated with donepezil. Donepezil (1 mg/kg p.o.) was administered for four weeks, starting one week after the ovariectomy. The serum concentrations of CTX-I, osteocalcin and other biochemical parameters, bone mass, density, mineralization, histomorphometric parameters and mechanical properties, and skeletal muscle mass and strength were examined. Estrogen deficiency increased bone resorption and formation and worsened cancellous bone mechanical properties and histomorphometric parameters. In NOVX rats, donepezil decreased bone volume to tissue volume ratio in the distal femoral metaphysis, increased the serum phosphorus concentration and tended to decrease skeletal muscle strength. No significant bone effects of donepezil were observed in OVX rats. The results of the present study indicate slightly unfavorable effects of donepezil on the musculoskeletal system in rats with normal estrogen levels.

The Effects of Prolonged Treatment with Cemtirestat on Bone Parameters Reflecting Bone Quality in Non-Diabetic and Streptozotocin-Induced Diabetic Rats.

Cemtirestat, a bifunctional drug acting as an aldose reductase inhibitor with antioxidant ability, is considered a promising candidate for the treatment of diabetic neuropathy. Our study firstly examined the effects of prolonged cemtirestat treatment on bone parameters reflecting bone quality in non-diabetic rats and rats with streptozotocin (STZ)-induced diabetes. Experimental animals were assigned to four groups: non-diabetic rats, non-diabetic rats treated with cemtirestat, diabetic rats, and diabetic rats treated with cemtirestat. Higher levels of plasma glucose, triglycerides, cholesterol, glycated hemoglobin, magnesium, reduced femoral weight and length, bone mineral density and content, parameters characterizing trabecular bone mass and microarchitecture, cortical microarchitecture and geometry, and bone mechanical properties were determined in STZ-induced diabetic versus non-diabetic rats. Treatment with cemtirestat did not affect all aforementioned parameters in non-diabetic animals, suggesting that this drug is safe. In diabetic rats, cemtirestat supplementation reduced plasma triglyceride levels, increased the Haversian canal area and slightly, but insignificantly, improved bone mineral content. Nevertheless, the insufficient effect of cemtirestat treatment on diabetic bone disease does not support its use in the therapy of this complication of type 1 diabetes mellitus.

Long-Term Cola Intake Does Not Cause Evident Pathological Alterations in the Femoral Bone Microstructure: An Animal Study in Adult Mice.

Short-term animal experiments and association studies in humans have shown that cola intake may have a detrimental impact on bone mineral density (BMD); however, other bone parameters have not been investigated. This study examined the effects of long-term cola consumption on the femoral bone microstructure using adult mice (n = 32) as an animal model, which were divided into water and cola groups depending on whether they received water or cola along with a standard rodent diet for 6 months. Micro-computed tomography revealed that cola intake did not significantly affect all measured parameters characterizing trabecular bone mass and microarchitecture, as well as cortical microarchitecture and geometry in both sexes, although a slight deterioration of these parameters was noted. Cola consumption also resulted in a slightly, statistically insignificant worsening of bone mechanical properties. In contrast to female mice, males receiving cola had a lower area of primary osteons' vascular canals. Nevertheless, long-term cola intake did not cause evident pathological alterations in the femur of adult mice, possibly due to a balanced diet and no restriction of physical activity. Therefore, the adverse effects of cola consumption on BMD, the only bone parameter studied so far, may be caused by other risk and lifestyle factors.

Unfavorable effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on the skeletal system of nondiabetic rats.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs, acting by inhibiting the reabsorption of glucose in the kidneys. They turned out to improve cardiovascular and renal outcomes not only in patients with type 2 diabetes but also in nondiabetic patients. At present, they are more and more widely used in patients without diabetes. Since there were concerns that SGLT2 inhibitors may increase fracture risk in diabetes, the aim of the study was to examine the effect of dapagliflozin and canagliflozin on the musculoskeletal system of nondiabetic, healthy rats. The experiments were carried out on mature female rats, divided into the control rats and rats treated with dapagliflozin (1.4 mg/kg p.o.) or canagliflozin (4.2 mg/kg p.o.) for 4 weeks. Serum bone turnover markers, skeletal muscle strength and mass, bone mass, density, histomorphometric parameters and mechanical properties were determined. Administration of the drugs did not affect the skeletal muscle mass and strength. There was no effect on serum bone turnover markers, and bone mass and composition. However, administration of both drugs resulted in disorders of cancellous bone microarchitecture and worsening of bone mechanical properties. In conclusion, both SGLT2 inhibitors unfavorably affected the skeletal system of healthy rats.

Effect of Administration of Azithromycin and/or Probiotic Bacteria on Bones of Estrogen-Deficient Rats.

The gut microbiota plays an important role in maintaining homeostasis, including that of the skeletal system. Antibiotics may affect the skeletal system directly or indirectly by influencing the microbiota. Probiotic bacteria have been reported to favorably affect bones in conditions of estrogen deficiency. The aim of this study was to investigate the effects of azithromycin (AZM) administered alone or with probiotic bacteria (Lactobacillus rhamnosus; LR) on bones in estrogen-deficient rats. The experiments were carried out on mature rats divided into five groups: non-ovariectomized (NOVX) control rats, ovariectomized (OVX) control rats, and OVX rats treated with: LR, AZM, or AZM with LR. The drugs were administered for 4 weeks. Serum biochemical parameters, bone mineralization, histomorphometric parameters, and mechanical properties were examined. Estrogen deficiency increased bone turnover and worsened cancellous bone microarchitecture and mechanical properties. The administration of LR or AZM slightly favorably affected some skeletal parameters of estrogen-deficient rats. The administration of AZM with LR did not lead to the addition of the effects observed for the separate treatments, indicating that the effects could be microbiota-mediated.

Lack of berberine effect on bone mechanical properties in rats with experimentally induced diabetes.

Multidirectional health-promoting activities of some plant-derived substances make them candidates for drugs used in diabetes and its complications such as osteoporosis. Berberine is a compound for which both antidiabetic and antiosteoporotic effects have been documented. The aim of the study was to investigate the effects of berberine on the skeletal disorders induced by experimental type 1 diabetes in rats. The experiments were performed on 3-month-old female rats, divided into three groups: I - healthy control rats, II - diabetic control rats, III - diabetic rats receiving berberine. Diabetes was induced by a single streptozotocin injection. Berberine administration (50 mg/kg/day p.o.) started two weeks later and lasted four weeks. Serum bone turnover markers and other biochemical parameters, bone mass and mineralization, histomorphometric parameters and mechanical properties were studied. Diabetes induced strong disorders of bone turnover, bone microarchitecture, and strength of cancellous bone. Berberine counteracted the effect of diabetes on the bone formation marker (osteocalcin) concentration, the growth plate, and some parameters of cancellous bone microarchitecture, but did not improve bone mineralization and bone mechanical properties in the diabetic rats. The lack of effect of berberine on bone quality does not support its use in the prevention of diabetes-induced bone damage.

Potential of Caffeine in Alzheimer's Disease-A Review of Experimental Studies.

Alzheimer's disease (AD) is the most common type of dementia leading to progressive memory loss and cognitive impairment. Considering that pharmacological treatment options for AD are few and not satisfactory, increasing attention is being paid to dietary components that may affect the development of the disease. Such a dietary component may be caffeine contained in coffee, tea or energy drinks. Although epidemiological data suggest that caffeine intake may counteract the development of cognitive impairment, results of those studies are not conclusive. The aim of the present study is to review the existing experimental studies on the efficacy of caffeine against AD and AD-related cognitive impairment, focusing on the proposed protective mechanisms of action. In conclusion, the reports of studies on experimental AD models generally supported the notion that caffeine may exert some beneficial effects in AD. However, further studies are necessary to elucidate the role of caffeine in the effects of its sources on cognition and possibly AD risk.

Negligible Effect of Estrogen Deficiency on Development of Skeletal Changes Induced by Type 1 Diabetes in Experimental Rat Models.

Although postmenopausal osteoporosis often occurs concurrently with diabetes, little is known about interactions between estrogen deficiency and hyperglycemia in the skeletal system. In the present study, the effects of estrogen deficiency on the development of biochemical, microstructural, and mechanical changes induced by streptozotocin-induced diabetes mellitus (DM) in the rat skeletal system were investigated. The experiments were carried out on nonovariectomized (NOVX) and ovariectomized (OVX) control and diabetic mature female Wistar rats. Serum levels of bone turnover markers (CTX-I and osteocalcin) and 23 cytokines, bone mass and mineralization, histomorphometric parameters, and mechanical properties of cancellous and compact bone were determined. The results were subjected to two-way ANOVA and principal component analysis (PCA). Estrogen deficiency induced osteoporotic changes, with increased bone resorption and formation, and worsening of microstructure (femoral metaphyseal BV/TV decreased by 13.0%) and mechanical properties of cancellous bone (the maximum load in the proximal tibial metaphysis decreased by 34.2%). DM in both the NOVX and OVX rats decreased bone mass, increased bone resorption and decreased bone formation, and worsened cancellous bone microarchitecture (for example, the femoral metaphyseal BV/TV decreased by 17.3% and 18.1%, respectively, in relation to the NOVX controls) and strength (the maximum load in the proximal tibial metaphysis decreased by 35.4% and 48.1%, respectively, in relation to the NOVX controls). Only in the diabetic rats, profound increases in some cytokine levels were noted. In conclusion, the changes induced by DM in female rats were only slightly intensified by estrogen deficiency. Despite similar effects on bone microstructure and strength, the influence of DM on the skeletal system was based on more profound systemic homeostasis changes than those induced by estrogen deficiency.

Effect of Berberine on Glycation, Aldose Reductase Activity, and Oxidative Stress in the Lenses of Streptozotocin-Induced Diabetic Rats In Vivo-A Preliminary Study.

Diabetes mellitus affects the eye lens, leading to cataract formation by glycation, osmotic stress, and oxidative stress. Berberine, an isoquinoline alkaloid, is a natural compound that has been reported to counteract all these pathological processes in various tissues and organs. The goal of this study was to evaluate whether berberine administered at a dose of 50 mg/kg by oral gavage for 28 days to rats with streptozotocin-induced diabetes reveals such effects on the biochemical parameters in the lenses. For this purpose, the following lenticular parameters were studied: concentrations of soluble protein, non-protein sulfhydryl groups (NPSH), advanced oxidation protein products (AOPP), advanced glycation end-products (AGEs), thiobarbituric acid reactive substances (TBARS), and activities of aldose reductase (AR), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Diabetes induced unfavorable changes in the majority of the examined parameters. The administration of berberine resulted in an increased soluble protein level, decreased activity of AR, and lowered AOPP and AGEs levels. The results suggest that berberine administered orally positively affects the lenses of diabetic rats, and should be further examined with regard to its anticataract potential.

Effects of diosgenin on the skeletal system in rats with experimental type 1 diabetes.

There is a great interest in substances of plant origin, which may exert health-promoting activities in diabetes and its complications. Previous studies suggested that diosgenin may favorably affect both glucose metabolism and osteoporosis. The aim of the study was to investigate the effects of diosgenin on the skeletal disorders induced by experimental type 1 diabetes (T1D) in rats. The experiments were performed on 3-month-old female rats, divided into three groups: I - healthy control rats, II - streptozotocin-induced diabetic control rats, III - diabetic rats receiving diosgenin. T1D was induced by a single streptozotocin injection (60 mg/kg i.p.). Diosgenin administration (50 mg/kg/day p.o.) started two weeks later and lasted four weeks. Serum bone turnover markers and other biochemical parameters, bone mass and mineralization, mechanical properties and histomorphometric parameters were examined. Diabetes induced profound metabolic disturbances and disorders of cancellous bone microarchitecture and strength. Diosgenin did not favorably affect the serum bone turnover markers and other biochemical parameters, bone mass, mineralization and mechanical properties in the diabetic rats. However, it counteracted the effect of diabetes on the growth plate and cancellous bone microarchitecture in the distal femur, indicating some limited beneficial influence on the skeleton.

Effects of loratadine, a histamine H1 receptor antagonist, on the skeletal system of young male rats.

BACKGROUND: Histamine H1 receptor antagonists are widely used in the treatment of allergic diseases. H1 receptors are expressed on bone cells and histamine takes part in regulation of bone metabolism. Loratadine is often prescribed to children. PURPOSE: The aim of the present study was to investigate the effects of loratadine on the skeletal system of young rats. MATERIAL AND METHODS: Loratadine (0.5, 5, and 50 mg/kg p.o. daily) was administered for 4 weeks to male Wistar rats, 6-week-old at the start of the experiment. Bone mass, mass of bone mineral, calcium, and phosphorus content in the bone mineral of the tibia, femur, and L-4 vertebra, histomorphometric parameters of the femur, mechanical properties of the proximal tibial metaphysis, femoral diaphysis and femoral neck, and serum levels of bone turnover markers were examined. RESULTS: Loratadine at 0.5 and 5 mg/kg did not significantly affect the skeletal system of young rats. At 50 mg/kg, loratadine decreased the femoral length, increased content of calcium and phosphorus in the bone mineral of the vertebra, and tended to improve mechanical properties of the tibial metaphysis. CONCLUSION: High-dose loratadine slightly but significantly affected development of the skeletal system in rapidly growing rats.

Effect of caffeine on biomarkers of oxidative stress in lenses of rats with streptozotocin-induced diabetes.

INTRODUCTION: One of the major causes of cataract in diabetes is oxidative stress induced by reactive oxygen species (ROS). Nowadays, new substances with antioxidative properties that may prevent cataract development are needed. One such substance is caffeine - an alkaloid with well-documented antioxidative activity. MATERIAL AND METHODS: The study was conducted on lenses obtained from female rats, divided into 3 groups: control rats; diabetic rats; diabetic rats treated with caffeine at a dose of 20 mg/kg p.o. Type 1 diabetes was induced by streptozotocin (60 mg/kg i.p.). After 4 weeks of caffeine administration, the rats were sacrificed, and the lenses were collected, weighed and homogenized in PBS. The homogenate was used for analysis of protein content, glutathione (GSH) concentration, advanced oxidation protein product (AOPP) concentration, malondialdehyde (MDA) concentration and the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). RESULTS: The SOD, CAT and GPx activities were found to be higher in the lenses of diabetic rats. There were also increased MDA and AOPP concentrations as well as decreased GSH concentration. The administration of caffeine resulted in decreased activity of SOD, CAT and GPx. The treatment with caffeine also caused an increase of GSH concentration and a decrease of MDA and AOPP concentrations. CONCLUSIONS: The results of the present study may be of relevance in determining the effect of caffeine on the processes induced by ROS in vivo. Further, they can be an indication for clinical observations aiming at the assessment of both preventive and therapeutic effects of caffeine in cataract.

Effect of Rosmarinic Acid on the Serum Parameters of Glucose and Lipid Metabolism and Oxidative Stress in Estrogen-Deficient Rats.

Rosmarinic acid is found in medicinal and spice plants such as rosemary, lemon balm, and mint. The aim of the study was to investigate the effect of rosmarinic acid on parameters of glucose and lipid metabolism and parameters of oxidative stress in rats in the early phase of estrogen deficiency. The study was carried out on mature female Wistar rats divided into the following groups: sham-operated control rats, ovariectomized control rats, and ovariectomized rats treated orally with rosmarinic acid at a dose of 10 mg/kg or 50 mg/kg daily for 28 days. The concentration of sex hormones, parameters related to glucose and lipid metabolism as well as parameters of antioxidant abilities and oxidative damage were determined in the blood serum. In the ovariectomized control rats, the homeostasis model assessment of insulin resistance (HOMA-IR) index and cholesterol concentration increased, the superoxide dismutase activity increased, and the reduced glutathione concentration decreased. Administration of rosmarinic acid at both doses induced decreases in the fructosamine concentration and HOMA-IR, an increase in the concentration of reduced glutathione, and a decrease in the concentration of advanced oxidation protein products in ovariectomized rats. Moreover, rosmarinic acid at a dose of 50 mg/kg induced a decrease in the total cholesterol and triglyceride concentrations. The results indicate that rosmarinic acid may be useful in the prevention of metabolic disorders associated with estrogen deficiency, however further studies are necessary.

Phloridzin, an Apple Polyphenol, Exerted Unfavorable Effects on Bone and Muscle in an Experimental Model of Type 2 Diabetes in Rats.

It is believed that apple fruits contain components with health-promoting effects, including some antidiabetic activity. One of the most known apple compounds is phloridzin, a glucoside of phloretin. Phloridzin and phloretin were reported to exert some favorable skeletal effects in estrogen-deficient rats and mice. The aim of the study was to investigate the effects of phloridzin on musculoskeletal system in rats with type 2 diabetes induced by a high-fat diet (HFD) and streptozotocin (STZ). The experiments were performed on mature female Wistar rats, divided into control rats (fed a standard laboratory diet), HFD/STZ control rats, and HFD/STZ rats receiving phloridzin (20 or 50 mg/kg/day per os) for four weeks. Serum biochemical parameters, muscle mass and strength, bone mass, density, histomorphometric parameters and mechanical properties were determined. The HFD/STZ rats developed hyperglycemia, with decreases in the muscle mass and strength and profound osteoporotic changes. Phloridzin at 20 mg/kg markedly augmented the unfavorable effects of diabetes on the muscle mass and strength and decreased growth of bones, whereas, at 50 mg/kg, it did not affect most of the investigated musculoskeletal parameters. Results of the study indicate the possibility of unfavorable effects of phloridzin on the musculoskeletal system in conditions of hyperglycemia.

The Effects of Sinapic Acid on the Development of Metabolic Disorders Induced by Estrogen Deficiency in Rats.

Sinapic acid is a natural phenolic acid found in fruits, vegetables, and cereals, exerting numerous pharmacological effects. The aim of the study was to investigate the influence of sinapic acid on biochemical parameters related to glucose and lipid metabolism, as well as markers of antioxidant abilities and parameters of oxidative damage in the blood serum in estrogen-deficient rats. The study was performed on 3-month-old female Wistar rats, divided into 5 groups, including sham-operated control rats, ovariectomized control rats, and ovariectomized rats administered orally with estradiol (0.2 mg/kg) or sinapic acid (5 and 25 mg/kg) for 28 days. The levels of estradiol, progesterone, interleukin 18, insulin, glucose, fructosamine, lipids, and enzymatic and nonenzymatic antioxidants (superoxide dismutase, catalase, and glutathione); total antioxidant capacity; and oxidative damage parameters (thiobarbituric acid-reactive substances, protein carbonyl groups, and advanced oxidation protein products) were determined in the serum. Estradiol counteracted the carbohydrate and cholesterol metabolism disorders induced by estrogen deficiency. Sinapic acid increased the serum estradiol concentration; decreased insulin resistance and the triglyceride and total cholesterol concentrations; and favorably affected the parameters of antioxidant abilities (reduced glutathione, superoxide dismutase) and oxidative damage (advanced oxidation protein products).

Caffeine at a Moderate Dose Did Not Affect the Skeletal System of Rats with Streptozotocin-Induced Diabetes.

Diabetes may lead to the development of osteoporosis. Coffee drinking, apart from its health benefits, is taken into consideration as an osteoporosis risk factor. Data from human and animal studies on coffee and caffeine bone effects are inconsistent. The aim of the study was to investigate effects of caffeine at a moderate dose on the skeletal system of rats in two models of experimental diabetes induced by streptozotocin. Effects of caffeine administered orally (20 mg/kg aily for four weeks) were investigated in three-month-old female Wistar rats, which, two weeks before the start of caffeine administration, received streptozotocin (60 mg/kg, intraperitoneally) alone or streptozotocin after nicotinamide (230 mg/kg, intraperitoneally). Bone turnover markers, mass, mineral density, histomorphometric parameters, and mechanical properties were examined. Streptozotocin induced diabetes, with profound changes in the skeletal system due to increased bone resorption and decreased bone formation. Although streptozotocin administered after nicotinamide induced slight increases in glucose levels at the beginning of the experiment only, slight, but significant unfavorable changes in the skeletal system were demonstrated. Administration of caffeine did not affect the investigated skeletal parameters of rats with streptozotocin-induced disorders. In conclusion, caffeine at a moderate dose did not exert a damaging effect on the skeletal system of diabetic rats.

Effects of fenoterol on the skeletal system depend on the androgen level.

BACKGROUND: The role of sympathetic nervous system in the osseous tissue remodeling is not clear enough. METHODS: The effects of fenoterol, a selective ß2-adrenomimetic drug, on the skeletal system of normal and androgen deficient (orchidectomized) rats were studied in vivo. Osteoclastogenesis and mRNA expression in osteoblasts were investigated in vitro in mouse cell cultures. RESULTS: Fenoterol administered to animals with physiological androgen level unfavorably affected the skeletal system, damaging the bone microarchitecture. Androgen deficiency induced osteoporotic changes, and fenoterol protected the osseous tissue from consequences of androgen deficiency. The results of in vitro studies correlated with the in vivo observations. A significantly increased number of osteoclasts in bone marrow cell cultures to which testosterone and fenoterol were added simultaneously was demonstrated. In cultures without the addition of testosterone, fenoterol significantly inhibited osteoclastogenesis in comparison with control cultures. CONCLUSIONS: The results indicate the favorable action of fenoterol in conditions of testosterone deficiency, and its destructive influence upon the skeleton in the presence of androgens. The results confirm the key role of sympathetic nervous system in the regulation of bone remodeling.

Opioid receptor agonists may favorably affect bone mechanical properties in rats with estrogen deficiency-induced osteoporosis.

The results of epidemiological, clinical, and in vivo and in vitro experimental studies on the effect of opioid analgesics on bone are inconsistent. The aim of the present study was to investigate the effect of morphine (an agonist of opioid receptors), buprenorphine (a partial µ opioid receptor agonist and κ opioid receptor antagonist), and naloxone (an antagonist of opioid receptors) on the skeletal system of female rats in vivo. The experiments were carried out on 3-month-old Wistar rats, divided into two groups: nonovariectomized (intact; NOVX) rats and ovariectomized (OVX) rats. The bilateral ovariectomy was performed 7 days before the start of drug administration. Morphine hydrochloride (20 mg/kg/day s.c.), buprenorphine (0.05 mg/kg/day s.c.), or naloxone hydrochloride dihydrate (2 mg/kg/day s.c.) were administered for 4 weeks to NOVX and OVX rats. In OVX rats, the use of morphine and buprenorphine counteracted the development of osteoporotic changes in the skeletal system induced by estrogen deficiency. Morphine and buprenorphine beneficially affected also the skeletal system of NOVX rats, but the effects were much weaker than those in OVX rats. Naloxone generally did not affect the rat skeletal system. The results confirmed the role of opioid receptors in the regulation of bone remodeling processes and demonstrated, in experimental conditions, that the use of opioid analgesics at moderate doses may exert beneficial effects on the skeletal system, especially in estrogen deficiency.

Effect of diosgenin, a steroidal sapogenin, on the rat skeletal system.

Diosgenin is a steroidal sapogenin present in fenugreek and Dioscorea spp. as glycosides (saponins). Diosgenin has already been reported to inhibit osteoclastogenesis and to stimulate osteogenic activity of osteoblastic cells in vitro, and to exert some antiosteoporotic effects in rats in vivo. The aim of the present study was to investigate the effects of diosgenin administration on the skeletal system of rats with normal estrogen level and with estrogen deficiency induced by bilateral ovariectomy. The experiments were carried out on 3-month-old non-ovariectomized and ovariectomized Wistar rats, divided into control rats and rats receiving diosgenin (50 mg/kg p.o. daily) for 4 weeks. Serum bone turnover markers, bone mass and mineralization, histomorphometric parameters and mechanical properties were studied. Diosgenin improved some investigated parameters in both non-ovariectomized and ovariectomized rats, in which estrogen deficiency induced osteoporotic changes. Diosgenin increased compact bone formation and probably inhibited cancellous bone resorption, which led to improvement of mechanical properties of compact and cancellous bone. In conclusion, this in vivo study demonstrated that diosgenin may be one of sparse compounds increasing bone formation.