Association of bone mineral density and potential risk factors for osteoporosis in patients with severe haemophilia A.

INTRODUCTION: In people with haemophilia (PWH), recurrent episodes of bleeding lead to joint deterioration and bone resorption. To date, the effects of various other factors on bone mineral density (BMD) reduction have found conflicting results. AIM: The aim of this study was to analyse the relationships between BMD, bone mineral content (BMC), and trabecular bone score (TBS) parameters based on the dual X-ray absorptiometry method (DXA) and potential risk factors for osteoporosis in patients with severe haemophilia A. METHODS: Fifty-five men with severe haemophilia A, aged 18-68 years, and 59 healthy volunteer men were enrolled in this study. Densitometric-derived lumbar spine and femoral neck BMD, BMC, and TBS were measured. Blood analyses were performed for morphology parameters, liver and kidney function parameters, and viral status. Serum levels of oestradiol (E2 ), testosterone (T), dehydroepiandrosterone sulphate (DHEA-S), parathormone, and vitamin D were measured. RESULTS: Patients showed significantly lower BMD compared to controls (p < .003). The result below the expected range for age was nearly double (6.82% vs. 3.92%) in PWH under 50 years old compared to controls. Haemophilic patients also exhibited significantly higher vitamin D3 deficiency (p < .0001), which was strongly associated with low TBS. Additionally, low body mass index and high neutrophil/lymphocyte ratio were correlated with low BMC and BMD. CONCLUSIONS: This study confirms the prevalence of low BMD and BMC in patients with haemophilia in Poland. Factors that contribute to low BMD are primarily vitamin D deficiency, low BMI, high neutrophil/lymphocyte ratio, and low testosterone/oestradiol ratio.

Long-term administration of fenspiride has no negative impact on bone mineral density and bone turnover in young growing rats.

BACKGROUND: Fenspiride is an antagonist of H1-histamine receptors that is used to treat acute and chronic respiratory tract infections and otitis media in children and adolescents. OBJECTIVES: The aim of the study was to assess the influence of long-term administration of fenspiride on bone mineral density (BMD) and bone turnover in young growing rats. MATERIAL AND METHODS: The experiment was carried out on 18 young (8-week-old) male Wistar rats receiving either fenspiride 15 mg/kg intragastrically (ig) (group F) or saline solution 4 mL/kg ig (group C) for 3 months. On days 1 and 93, blood samples were collected and serum levels of calcium, phosphorus and markers of bone turnover were measured. On days 2 and 92, BMD was measured with dual-energy x-ray absorptiometry (DXA) using small animal software. RESULTS: We detected no influence of fenspiride on weight gain, total body BMD (0.212 ±0.010 g/cm2 vs 0.204 ±0.024 g/cm2), hind limb BMD (0.264 ±0.016 g/cm2 vs 0.252 ±0.027 g/cm2), or bone macroscopic parameters. There were no significant differences between group F and group C in serum levels of osteocalcin (group F: 0.42 ±0.09 ng/mL vs group C: 0.43 ±0.08 ng/mL), C-terminal telopeptide of type I collagen (F: 0.31 ±0.08 ng/mL vs C: 0.29 ±0.08 ng/mL), osteoprotegerin (F: 5.47 ±0.78 pg/mL vs C: 5.35 ±1.65 pg/mL), receptor activator of nuclear factor kappa B ligand (F: 0.65 ±0.85 pg/mL vs C: 0.56 ±0.86 pg/mL), parathormone (F: 237 ±182 pg/mL vs C: 289 ±200 pg/mL), total calcium (F: 6.38 ±1.50 mg/dL vs C: 6.83 ±1.71 mg/dL), or inorganic phosphorus (F: 5.19 ±1.76 mg/dL vs C: 5.50 ±1.32 mg/dL). CONCLUSIONS: Long-term administration of fenspiride has no negative impact on BMD and bone metabolism in young growing rats.

Effect of long-term administration of ranitidine, a histamine H2 receptor antagonist, on bone metabolism in young growing rats.

BACKGROUND: Histamine regulates function of osteoclasts and osteoblasts, however data regarding the influence of histamine H2 receptors antagonists on bone tissue are ambiguous. Factors that influence growing skeleton may have an important impact on the peak bone mass and future risk of fractures. The aim of our study was the assessment of influence of ranitidine, on growing bones. METHODS: The experiment was carried out on young male Wistar rats divided into two groups receiving either ranitidine (10mg/kg ip) or vehicle. RESULTS: A significant decrease in femoral BMD in ranitidine-treated rats (R) compared to vehicle-treated ones (C) was detected (0.262±0.009g/cm2vs. 0.271 ±0.007g/cm2, p<0.05). In group R we observed elevated serum C-terminated telopeptide of type I collagen (CTX) level with concomitantly lowered serum osteocalcin (OC) concentration comparing to control group (151.2±27.2pg/ml vs. 101.5±55.6, p<0.05 and 229.1±50.0pg/ml vs. 292.0±52.9, p<0.05, respectively). Serum concentration of inorganic phosphorus was lower in group R than in group C (134±13mmol/L vs. 157±28mmol/L, p<0.05). CONCLUSIONS: Long-term administration of ranitidine increases bone resorption and decreases bone formation in growing rats leading to decrease in BMD.

Oral administration of kaempferol inhibits bone loss in rat model of ovariectomy-induced osteopenia.

BACKGROUND: Postmenopausal osteoporosis and osteoporotic fractures constitute an increasing problem in developing countries. Kaempferol, isolated from seeds of Cuscuta chinensis, is an active flavonoid inhibiting in vitro osteoclast activity. The aim of the presented research was an assessment of kaempferol effect on estrogen-deficiency-induced bone structure disturbances in rats. METHODS: The study was performed on 24 Wistar female rats divided into 3 groups: SHAM - rats undergoing a "sham" surgery, OVX-C - control group of animals that underwent ovariectomy, OVX-K - rats undergoing ovariectomy and receiving kaempferol for 8 weeks (from day 56 to day 112). RESULTS: In the OVX-K group, contrary to the OVX-C one, there was no significant decrease in femoral bone mineral density (BMD). A significant increase in Young's modulus was observed in the OVX-K group compared to the OVX-C (15.33±2.51GPa vs. 11.14±1.93GPa, p<0.05). A decreased bone turnover was detected in the OVX-K group. Tissue volume ratio (BV/TV) and trabecular bone perimeter were increased in the OVX-K group compared to the OVX-C one (0.241±0.037 vs. 0.170±0.022, p<0.05 and 15.52±2.78mm vs. 9.67±3.07mm, p<0.05, respectively). CONCLUSION: Kaempferol has a beneficial influence on estrogen-deficiency-induced disturbances of bone structure in rats.

Effects of long-term administration of pantoprazole on bone mineral density in young male rats.

BACKGROUND: Epidemiological studies suggest that long-term administration of proton pump inhibitors (PPIs) may decrease bone mineral density (BMD) and increase the risk of osteoporotic fractures. The aim of the study was to assess the influence of pantoprazole on bone metabolism in growing rats. METHODS: The experiment was carried out on twenty-four young male Wistar rats divided into two groups receiving either pantoprazole at the dose of 3mg/kg or vehicle for 12 weeks. Femoral bone mineral density (BMD) and bone histomorphometry were assessed. Serum total calcium, inorganic phosphate and markers of bone turnover were measured. RESULTS: In pantoprazole-treated rats a decreased BMD was detected (0.2618±0.0133g/cm(2)vs. 0.2715±0.0073g/cm(2), p<0.05). Bone histomorphometry revealed a decrease in growth plate thickness (G.Pl.RTh.) (161.0±27.8µm vs. 195.0±20.8, p<0.05) in pantoprazole-treated animals. Serum total calcium level and osteocalcin concentrations were decreased in the pantoprazole-treated group (9.62±0.55mg/dl vs. 10.15±0.38mg/dl, p<0.05 and 242.7±44.4pg/ml vs. 342.5±123.3pg/ml, p<0.05, respectively). CONCLUSION: We observed that PPIs might have a negative impact on bone formation in growing rats mainly due to their inhibitory effects on the gastric proton pump, with probable deterioration of calcium absorption and decrease in growth plate thickness.