Significant Changes In Bone Density Research Articles

Accelerated turnover of metaphyseal trabecular bone in mice overexpressing cathepsin K.

This study is based on a hypothesis that overexpression of an osteoclast enzyme, cathepsin K, causes an imbalance in bone remodeling toward bone loss. The hypothesis was tested in transgenic (TG) mice harboring additional copies of the murine cathepsin K gene (Ctsk) identifiable by a silent mutation engineered into the construct. For this study, three TG mouse lines harboring 3-25 copies of the transgene were selected. Tissue specificity of transgene expression was determined by Northern analysis, which revealed up to 6-fold increases in the levels of cathepsin K messenger RNA (mRNA) in calvarial and long bone samples of the three TG lines. No changes were seen in the mRNA levels of other osteoclast enzymes, indicating that the increase in cathepsin K mRNA was not a reflection of activation of all osteoclast enzymes. Immunohistochemistry confirmed that cathepsin K expression in the TG mice was confined to osteoclasts and chondroclasts. Histomorphometry revealed a significantly decreased trabecular bone volume (BV), but, surprisingly, also a marked increase in the number of osteoblasts, the rate of bone turnover, and the amount of mineralizing surface (MS). However, monitoring of bone density in the proximal tibias of the TG mice with peripheral quantitative computed tomography (pQCT) failed to reveal statistically significant changes in bone density. Similarly, no statistically significant alterations were observed in biomechanical testing at the age of 7 months. The increases in parameters of bone formation triggered by increased cathepsin K expression is an example of the tight coupling of bone resorption and formation during the bone-remodeling cycle.

Impact of antihypertensive therapy on the skeleton: effects of enalapril and AT1 receptor antagonist losartan in female rats

No data are available about the effects of AT1 receptor antagonist losartan on the skeleton and there is also little information on the activity of an ACE inhibitor enalapril on bone metabolism. It is widely believed that the vasculature plays an important role in bone remodeling under normal and pathological conditions. We treated 14-week-old female Wistar rats with losartan, enalapril or saline. Administration of the ACE inhibitor enalapril and angiotensin II antagonist losartan had no effect on total malondialdehyde (MDA) in the blood and on urinary excretion of some eicosanoids and their metabolites. The administration of enalapril and losartan in a dose recommended for the treatment of hypertension did not cause significant changes in bone density, the ash and mineral content or morphometric parameters of the femur compared to the values found in control female rats.

A randomized comparative study of the effect of leuprorelin acetate depot and danazol in the treatment of endometriosis: S.-P. Chang; H.-T. Ng Chin Med J (Taipei) 1996 57/6 (431–437)

Administration of superactive agonistic analog of gonadotropin-releasing hormone (GnRH) has shown to induce a paradoxic and reversible suppression of gonadotropins, so that gonadal steroid concentrations are suppressed and hypoestrogenemia is induced. In order to compare the efficacy and safety of leuprorelin acetate depot (LA) and danazol in the treatment of endometriosis, we conducted this study.A total of forty-five patients with pelvic endometriosis of different severity at laparoscopy with biopsy of peritoneal implants (n = 33) and surgical procedure (enucleation of ovarian chocolate cysts, cystectomy, or fulguration, n = 12) were included in the study and followed during the 20 weeks of treatment. LA 3.75 mg was injected subcutaneously every 28 days, while the daily oral dose of danazol was 800 mg.Both treatments were associated with a lowering of severity score. There was a consistent decrease in women with stage IV disease in the LA group and an increase in patients with stage I disease in the danazol group, but no difference was found between both treatments. Hot flushing was the most common side effect reported in 97% of LA but occurred only in 13% of danazol-treated patients. In contrast, the androgenic, anabolic side effects of weight gain and myalgia were common in those receiving danazol. The CA-125 levels were significantly lower in both treatment groups compared with their pretreatment levels (p < 0.01). During the five months of the LA treatment, biochemical evaluation revealed no pathologic alternation. Only total protein albumin, alkaline phosphatase, total bilirubin, total cholesterol, high density lipoprotein-cholesterol, low density lipoprotein-cholesterol, uric acid and calcium increased significantly. Danazol was also associated with adverse metabolic effects and significantly increased low-density lipoprotein-cholesterol concentrations (p < 0.05). In the fourth week, serum estradiol (E2) levels decreased to nearly castrated levels (13.87 +/- 1.63 pg/ml) in all patients treated with LA, and remained at this level thereafter. On the contrary, a slight but significant increase of the serum E2 levels was noted during the danazol treatment. After five months of treatment with LA, no significant changes in bone density were observed at the femoral neck or the anteroposterior (AP) view of lumbar spine, but there was a significant loss in bone density at the lateral view of lumbar spine (-7.1%, p < 0.05).Both LA and danazol are effective in the treatment of endometriosis. The hypoestrogenic side effects of LA may be better tolerated than the androgenic, anabolic effects of danazol. However, the danazol treatment costs less than LA and has no significant side effect with osteoporosis.

Gonadotropin-releasing hormone analog plus an oral contraceptive containing desogestrel in women with severe hirsutism: Effects on hair, bone, and hormone profile after 1-year use

To evaluate the usefulness of d-Trp-6-luteinizing hormone—releasing hormone (LHRH) (triptorelin), a gonadotropin-releasing hormone (GnRH) analog (GnRHa), plus an oral contraceptive (OC) in the treatment of severe hirsutism, a total of 48 women between 19 and 35 years of age suffering from polycystic ovary syndrome (PCOS) with severe hirsutism were studied. Hyperandrogenism of adrenal origin was excluded in all subjects. Twenty-three patients received 3.75 mg d-Trp-6-LHRH intramuscularly monthly for 1 year plus an OC containing 30 μg ethinyl-estradiol and 150 μg desogestrel. A second group of 25 subjects received an OC containing 35 μg ethinyl-estradiol and 2 mg cyproterone acetate (CPA). Immediately before and after months 6 and 12 of therapy, bone mineral density (BMD) and Ferriman-Gallwey scores were evaluated and follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), prolactin (PRL), testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS), 17-OH-progesterone (17-OHP), and sex hormone—binding globulin (SHBG) were determined. After 1 year of follow-up study, the combination of a GnRHa plus OC resulted in a decrease of hirsutism similar to that observed in the CPA group (41.9% v 40.5%) and in a suppression of gonadotropins and ovarian steroids in all treated women, without significant changes in bone density. The GnRHa-OC combination can potentially be used in the treatment of hirsutism and hyperandrogenism.

Topical calcipotriene has no short-term effect on calcium and bone metabolism of patients with psoriasis

Background: The biologically active form of vitamin D 3, calcitriol, is effective in the treatment of psoriasis but can alter calcium metabolism. Calcipotriene is an analog of calcitriol that has low calcemic activity and aids in clearing psoriasis. Objective: The purpose of this study was to determine the safety of topical therapy with calcipotriene particularly in relation to calcium and bone metabolism. Methods: In a double-blind, randomized, parallel, vehicle-controlled trial, 78 adults with plaque psoriasis were treated twice daily with topical calcipotriene ointment (50 μg/gm, maximum usage, 120 gm per week) or vehicle for 8 weeks. After a screening visit, patients were admitted to the hospital at weeks 0 (baseline), 1, 2, 4, and 8. Blood and urine chemistry analysis included parathyroid hormone, serum calcium, bone-specific alkaline phosphatase, urinary hydroxyproline, and 24 hour urinary calcium excretion. Bone densitometry measures were performed at baseline and week 8. Results: No incidences of calcipotriene treatment-related hypercalcemia, calcium mobilization from bone, or clinically significant changes in bone density were noted during this study. Conclusion: Topical application of up to 120 gm per week of calcipotriene ointment for 8 weeks is safe and effective for plaque psoriasis. There were no adverse effects on calcium and bone metabolism during this 8-week study.

Non-linear increase in vertebral density induced by a synthetic steroid (Org OD 14) in women with established osteoporosis

The results of a 2-year placebo-controlled study in 38 female patients with osteoporosis are presented. This study was conducted to evaluate the efficacy of a daily oral dose of 2.5 mg Org OD 14 ((7α,17α)-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one) in the treatment of established osteoporosis. Org OD 14 is a steroid which shows combined weak oestrogenic, androgenic and progestational activity. A total of 31 patients completed a 12-month study period (17 placebo. 14 Org OD 14) and 25 of these went on to complete the full 24-months (15 placebo, 10 Org OD 14). A significant increase in bone mineral density as measured by dual photon absorptiometry was recorded in the lumbar spine in the Org OD 14-treated patients at 8, 16 and 24 months. The gain in bone mass after 8 months averaged 4% ( P < 0.01) and after 24 months 8% ( P < 0.001). In the control group, a bone loss rate of 2% per year was recorded in the lumbar spine. No significant changes in bone density in the forearm as assessed by single photon absorptiometry were found in either group. The increase in spinal bone density in the Org OD 14 group was non-linear and followed an S-shaped upward pattern. Org OD 14, while inducing no appreciable endometrial stimulation, was found to be a bone-active compound with anti-resorbing as well as anabolic activity. Org OD 14 warrants consideration not only for the long-term prevention of bone loss but also for curative treatment of post-menopausal osteoporosis.

Effects of gonadotrophin-releasing hormone agonist on uterine fibroids and bone density

Bone density (BD) was evaluated by single photon absorptiometry (SPA) in 18 women treated with Buserelin a gonadotrophin-releasing hormone (LHRH) analogue, for uterine fibroids. Buserelin was administered for a period of 6 mth. Amenorrhoea and oestradiol levels in the follicular-phase range were recorded in all patients during treatment. Fibroid volume was evaluated by means of ultrasound. SPA was performed at the 1 3 proximal radius and at the 1 10 distal radius sites before starting therapy and every 2 mth subsequently for 12 mth. BD was also measured in a control group of 18 normally-menstruating premenopausal women, matched for age and body mass index. No significant changes in BD at the proximal or distal radius sites were observed in either the cases or the controls during the study. Moreover, comparison of the data on the cases and the controls revealed no differences in BD at 0, 6 or 12 mth. Thus, although LHRH analogue treatment proved effective in reducing fibroids, it did not cause any significant changes in BD.