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.

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.

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.

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.

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.

Effects of Trigonelline, an Alkaloid Present in Coffee, on Diabetes-Induced Disorders in the Rat Skeletal System.

Diabetes increases bone fracture risk. Trigonelline, an alkaloid with potential antidiabetic activity, is present in considerable amounts in coffee. The aim of the study was to investigate the effects of trigonelline on experimental diabetes-induced disorders in the rat skeletal system. Effects of trigonelline (50 mg/kg p.o. daily for four weeks) were investigated in three-month-old female Wistar rats, which, two weeks before the start of trigonelline administration, received streptozotocin (60 mg/kg i.p.) or streptozotocin after nicotinamide (230 mg/kg i.p.). Serum bone turnover markers, bone mineralization, and mechanical properties were studied. Streptozotocin induced diabetes, with significant worsening of bone mineralization and bone mechanical properties. Streptozotocin after nicotinamide induced slight glycemia increases in first days of experiment only, however worsening of cancellous bone mechanical properties and decreased vertebral bone mineral density (BMD) were demonstrated. Trigonelline decreased bone mineralization and tended to worsen bone mechanical properties in streptozotocin-induced diabetic rats. In nicotinamide/streptozotocin-treated rats, trigonelline significantly increased BMD and tended to improve cancellous bone strength. Trigonelline differentially affected the skeletal system of rats with streptozotocin-induced metabolic disorders, intensifying the osteoporotic changes in streptozotocin-treated rats and favorably affecting bones in the non-hyperglycemic (nicotinamide/streptozotocin-treated) rats. The results indicate that, in certain conditions, trigonelline may damage bone.

Exercise prevented the lansoprazole-induced reduction of anti-osteoporotic efficacy of alendronate in androgen deficiency rats.

Clinical studies indicate that proton pump inhibitors (PPIs), used long-term in elderly patients, increase the risk of osteoporotic fractures, and decrease the anti-fracture efficacy of alendronate. The aim of the present study was to examine the effect of physical exercise on the anti-osteoporotic efficacy of alendronate administered concurrently with lansoprazole, a PPI, in male rats with androgen deficiency induced by orchidectomy. Male Wistar rats at 3 months of age were divided into: sham-operated control rats, orchidectomized (ORX) control rats, ORX rats receiving alendronate, ORX rats receiving alendronate and lansoprazole, ORX rats receiving alendronate and subjected to exercise, and ORX rats receiving alendronate and lansoprazole and subjected to exercise. The orchidectomy or sham-operation was performed 7-8 days before the start of drug administration. The rats were subjected to the exercise on the treadmill 1 hour/day for 7 weeks (6 days a week). Alendronate sodium (3 mg/kg p.o.) and lansoprazole (4 mg/kg p.o.) were administered once daily for 7 weeks (6 days a week). Mechanical properties of the tibial metaphysis and femoral neck were assessed. Bone turnover markers, histomorphometric parameters, bone mass and mass of bone mineral were also studied. Lansoprazole weakened the anti-osteoporotic efficacy of alendronate. The exercise increased the alendronate effect. Similar changes were observed in the rats treated with lansoprazole and alendronate, subjected to exercise; no deleterious effects of lansoprazole were observed. In conclusion, the exercise prevented the lansoprazole-induced reduction the anti-osteoporotic efficacy of alendronate in orchidectomized rats.

Favorable effect of moderate dose caffeine on the skeletal system in ovariectomized rats.

SCOPE: Caffeine, a methylxanthine present in coffee, has been postulated to be responsible for an increased risk of osteoporosis in coffee drinkers; however, the data are inconsistent. The aim of the present study was to investigate the effects of a moderate dose of caffeine on the skeletal system of rats with normal and decreased estrogen level (developing osteoporosis due to estrogen deficiency). METHODS AND RESULTS: The experiments were carried out on mature nonovariectomized and ovariectomized Wistar rats, divided into control rats and rats receiving caffeine once daily, 20 mg/kg p.o., for 4 wk. Serum bone turnover markers, bone mass, mass of bone mineral, calcium and phosphorus content, histomorphometric parameters, and bone mechanical properties were examined. Caffeine favorably affected the skeletal system of ovariectomized rats, slightly inhibiting the development of bone changes induced by estrogen deficiency (increasing bone mineralization, and improving the strength and structure of cancellous bone). Moreover, it favorably affected mechanical properties of compact bone. There were no significant effects of caffeine in rats with normal estrogen levels. CONCLUSION: In conclusion, results of the present study indicate that low-to-moderate caffeine intake may exert some beneficial effects on the skeletal system of mature organisms.

Alendronate prevents development of the skeletal changes induced by azathioprine in rats.

Immunosuppressive drugs are known to disturb bone remodeling. Azathioprine (AZA) is a potent immunosuppressive drug, but its effect on the skeletal system has not been reported so far. The aim of the present study was to investigate the effect of AZA on the rat bone remodeling, and the effect of alendronate on development of skeletal changes induced by AZA. The experiments were carried out on 3-month-old male Wistar rats, divided into the following groups: C - control rats (distilled water), AZA - azathioprine, ALN - alendronate, AZA + ALN - azathioprine and alendronate. Azathioprine (4 mg/kg po), alendronate (3 mg/kg po) and distilled water (2 ml/kg po) were administered once daily for 28 days. Bone remodeling was estimated based on quantitative and histomorphometric evaluation of the tibia and femur, and the mechanical properties of the femur and femoral neck. AZA at a dose of 4 mg/kg for 28 days induced bone remodeling disorders, inhibiting bone formation and mineralization. Alendronate prevented the development of skeletal changes caused by AZA administration, inhibiting bone resorption and increasing bone mineralization.

Do effects of propranolol on the skeletal system depend on the estrogen status?

BACKGROUND: Propranolol, a nonselective ß-adrenergic receptor antagonist, was reported to favorably affect the skeletal system in different animal models. The aim of the study was to investigate whether the effects of propranolol on the skeletal system depend on the estrogen status. METHODS: The in vivo experiments were carried out on the following groups of mature female Wistar rats: sham-operated control rats, sham-operated rats receiving propranolol, ovariectomized (OVX) control rats, OVX rats receiving propranolol, OVX rats receiving estradiol, OVX rats receiving estradiol and propranolol. Propranolol hydrochloride (10 mg/kg po) and/or estradiol (0.1 mg/kg po) were administered daily for 4 weeks. Bone mass, mineral and calcium content, macrometric and histomorphometric parameters, and mechanical properties were examined. In vitro, effects of estradiol and propranolol on the formation of mouse osteoclasts and on the mRNA expression of genes related to osteoclastogenesis, bone formation and mineralization, as well as adrenergic and estrogen signalling in mouse osteoblasts were investigated. RESULTS AND CONCLUSION: Propranolol exerted some favorable effects on the rat skeletal system in vivo, independently of the estrogen status. However, in vitro studies indicated a possibility of some antagonistic relations between the estradiol and propranolol effects.

Proton pump (H+/K+-ATPase) inhibitors weaken the protective effect of alendronate on bone mechanical properties in estrogen-deficient rats.

BACKGROUND: Alendronate can induce esophagitis and stomach ulceration requiring the concurrent use of drugs which decrease HCl production. The aim of the present study was to investigate the effect of concurrent administration of proton pump inhibitors, omeprazole or pantoprazole, and alendronate on the mechanical properties of long bones in bilaterally ovariectomized (OVX) rats. METHODS: The experiments were carried out on 3-month-old Wistar rats, divided into following groups: non-ovariectomized control rats, OVX control rats, OVX rats administered omeprazole or pantoprazole, OVX rats administered alendronate, OVX rats administered alendronate and omeprazole or pantoprazole. The drugs were administered to the rats for 28 days: alendronate at a dose of 3mg/kg po, omeprazole or pantoprazole at a dose of 3mg/kg ip. Mechanical properties of tibialmetaphysis, femoral diaphysis and femoral neck were assessed. Bone macrometric parameters, mass and mass of bone mineral were also examined in the tibia and femur. RESULTS: Estrogen deficiency caused development of osteopenia with significant worsening of bone mechanical properties. Alendronate counteracted the deleterious changes in bone mechanical properties of the tibial metaphysis and femoral neck induced by estrogen deficiency. Pantoprazole worsened mechanical properties of the tibia in estrogen-deficient rats. Omeprazole or pantoprazole administered concurrently with alendronate attenuated the effect of alendronate on mechanical properties of the tibial metaphysis and femoral neck in ovariectomized rats. The unfavorable effect of pantoprazole was stronger than that of omeprazole. CONCLUSION: Proton pump inhibitors weakened the protective effect of alendronate on bone mechanical properties in estrogen-deficient rats.

Bone remodeling after administration of proton pump (H+/K+-ATPase) inhibitors and alendronate in ovariectomized rats.

During osteoporosis therapy with alendronate, esophagitis and stomach ulceration may occur, requiring the concurrent use of drugs which decrease gastric juice production. The aim of the present study was to investigate the effect of concurrent administration of proton pump (H+/K+ATP-ase) inhibitors: omeprazole or pantoprazole and alendronate on bone remodeling in ovariectomized rats. The experiments were carried out on 3-month-old Wistar rats, divided into following groups (n = 8-10): NOVX - non-ovariectomized control rats; OVX - ovariectomized control rats; OVX + alendronate; OVX + omeprazole; OVX + omeprazole + alendronate; OVX + pantoprazole; OVX + pantoprazole + alendronate. The drugs were administered for 28 days: alendronate (3 mg/kg p.o.), omeprazole or pantoprazole (3 mg/kg i.p.). Bone remodeling was estimated based on histomorphometric evaluation of the tibia (endosteal and periosteal transverse growth and the osteoid width, transverse cross-section surface of the diaphysis and of the marrow cavity) and the femur (width of trabeculae in the distal epiphysis and metaphysis). Bone mass/100 g body mass and mass of bone mineral/100 mg bone mass in the tibia and femur were also determined. Pantoprazole stronger than omeprazole intensified bone remodeling disorders caused by estrogen deficiency in ovariectomized rats. Bone remodeling disorders were the result of intensification of bone resorption with concurrent inhibition of bone formation and mineralization. Pantoprazole, and to lesser extent omeprazole, weakened the preventive effect of alendronate on bone remodeling in ovariectomized rats.

Effects of vigabatrin on the skeletal system of young rats.

Long-term administration of antiepileptic drugs may be connected with the risk of impairment of bone remodeling. Contrary to the reported unfavorable effect of classic antiepileptic drugs on bone metabolism, little is known about the effect of the next generation antiepileptics on bone remodeling. The aim of the present study was to investigate the effect of vigabatrin, as a representative of new antiepileptics, on the skeletal system of young rats, in comparison with conventional drugs--phenytoin and valproic acid. The experiments were carried out on 4-week-old male Wistar rats, divided into the control rats, and rats receiving vigabatrin (250 mg/kg p.o. daily), phenytoin (20 mg/kg p.o. daily) or valproic acid (250 mg/kg p.o. daily). The drugs were administered for 28 days. Histomorphometric parameters of the tibia and femur, mechanical properties of the femur, and bone length, diameter, mass, content of mineral substances and calcium were examined. After administration of phenytoin or valproic acid, the investigated bone parameters did not significantly differ from those observed in the control rats. Administration of vigabatrin caused profound impairment of bone accrual with impairment of bone histomorphometric parameters, along with the significant decrease in the body mass gain.

Effects of Extracts from Trifolium medium L. and Trifolium pratense L. on Development of Estrogen Deficiency-Induced Osteoporosis in Rats.

Some plant species belonging to Trifolium L. genus are a source of isoflavones considered to exert phytoestrogenic activities. The aim of the present study was to examine the effects of standardized extract obtained from aerial parts of Trifolium medium L., in comparison with the extract of Trifolium pratense L., on the development of estrogen deficiency-induced osteoporosis in rats. Both Trifolium extracts, at doses corresponding to 10 and 20 mg/kg of isoflavone aglycones daily, or estradiol (0.2 mg/kg daily), were administered orally to ovariectomized (OVX) rats for 4 weeks. Serum bone turnover markers, bone mass, mineralization, and mechanical properties were studied. In OVX control rats, mechanical properties of the tibial metaphysis and femoral neck were strongly worsened in comparison with sham-operated control rats, and those of femoral diaphysis were unaffected. Estradiol counteracted the worsening of the tibial strength and increases in bone turnover markers. Both extracts significantly increased the strength of the femoral diaphysis and calcium and phosphorus content in the bone mineral, but only T. pratense extract increased the strength of the tibial metaphysis. In conclusion, effects of both Trifolium extracts differed from those of estradiol. It is possible that other than isoflavone extract constituents contributed to their skeletal effects.

Effects of propranolol on the development of glucocorticoid-induced osteoporosis in male rats.

Glucocorticoid-induced osteoporosis is the most frequently occurring type of secondary osteoporosis. Antagonists of ß-adrenergic receptors are now considered to be potential drugs under investigation for osteoporosis. The aim of the present study was to investigate the effects of propranolol, a nonselective ß-receptor antagonist, on the skeletal system of mature male rats and on the development of bone changes induced by glucocorticoid (prednisolone) administration. The experiments were performed on 24-week-old male Wistar rats. The effects of prednisolone 21-hemisuccinate sodium salt (7 mg/kg, sc daily) or/and propranolol hydrochloride (10 mg/kg, ip daily) administered for 4 weeks on the skeletal system were studied. Bone and bone mineral mass in the tibia, femur and L-4 vertebra, length and diameter of the long bones, mechanical properties of tibial metaphysis, femoral diaphysis and femoral neck, bone histomorphometric parameters and turnover markers in serum were determined. Prednisolone-induced unfavorable skeletal changes led to disorders in bone mechanical properties. Propranolol not only did not improve bone parameters, but even caused deleterious effects on the skeletal system. Concurrent administration of propranolol with prednisolone did not counteract the changes induced by prednisolone. The results of this study may help to understand the equivocal results of human studies on the effects of ß-blockers on the skeletal system. It is possible that the drugs exert biphasic effects on the skeletal system, both favorable and deleterious, depending on the dose or individual susceptibility.

Fenoterol did not enhance glucocorticoid-induced skeletal changes in male rats.

Glucocorticoids and ß(2)-adrenergic receptor agonists are the most commonly used drugs in the treatment of asthma. Both therapies are potentially dangerous to the skeletal system. The aim of the present study was to investigate the effects of fenoterol, a ß(2)-receptor agonist, on the development of bone changes induced by glucocorticoid (prednisolone) administration in mature male rats. The experiments were carried out on 24-week-old male Wistar rats. The effects of prednisolone 21-hemisuccinate sodium salt (7 mg/kg s.c. daily) or/and fenoterol hydrobromide (1.4 mg/kg i.p. daily), administered for 4 weeks, on the skeletal system were studied. Bone turnover markers, geometric parameters, mass, mass of bone mineral in the tibia, femur and L-4 vertebra, bone histomorphometric parameters and mechanical properties of tibial metaphysis, femoral diaphysis and femoral neck were determined. Both prednisolone and fenoterol had damaging effects on the skeletal system of mature male rats. However, concurrent administration of fenoterol and prednisolone did not result in the intensification of the deleterious skeletal effect of either drug administered separately.