Previous studies demonstrated that intermittent treatment with PTH increases osteoblast number and bone formation in growing adult rats. The cellular mechanism for this increase was investigated 16-month-old female Continuous [3H]thymidine infusion over a 1-week [human PTH-(1-34)] period performed to determine the percentage of newly formed osteoblasts originate from progenitor cells. To verify formation, we histomorphometry Northern blot analysis selected matrix proteins. resulted dramatic...

Abstract The effects of ovariectomy for four weeks and 17β-estradiol three on histomorphometry the tibial diaphysis were determined in young rats. subcutaneous implants demineralized bone matrix also examined. Groups female rats either ovariectomized or sham operated. After surgery, animals weight matched pair fed. Despite same caloric intake, grew more rapidly than pair-fed, sham-operated controls but significantly heavier at sacrifice only one experiments. Ovariectomy did not change mean...

Abstract Substantial evidence does not support the prevailing view that leptin, acting through a hypothalamic relay, decreases bone accrual by inhibiting formation. To clarify mechanisms underlying regulation of architecture we evaluated growth and turnover in wild-type (WT) mice, leptin receptor-deficient db/db leptin-deficient ob/ob mice treated with leptin. We also performed gene therapy to determine effect elevated levels on osteoblasts. Finally, effects loss peripheral signaling...

Bone mineral density increases with fat body mass, and obesity has a protective effect against osteoporosis.However, the relationship between mass bone is only partially explained by combination of hormonal mechanical factors.Serum leptin levels are strongly directly related to mass.We report here effects administration compared estrogen therapy on ovariectomy-induced loss in rats.Leptin was effective at reducing trabecular loss, architectural changes, periosteal formation.Interestingly,...

PTH treatment can result in dramatic increases cancellous bone volume normal and osteopenic rats. However, this potentially beneficial response is only observed after pulsatile treatment; continuous infusion of leads to hypercalcemia abnormalities. The purpose these studies was determine the optimal duration pulses. A preliminary study revealed that human PTH-(1–34) (hPTH) cleared from circulation within 6 h sc administration an anabolic dose hormone (80μ g/kg). To establish effects...

We have developed an in vitro system, using embryonic chicken tibiae grown a serum-free medium, which exhibits simultaneous bone formation and resorption. Tibiae from 8-day embryos increased mean (+/- SD) length (4.0 +/- 0.4 to 11.0 0.3 mm) dry weight (0.30 0.04 0.84 mg) during 12 days vitro. There was incorporation of [3H]proline into hydroxyproline (120 20 340 cpm/mg per 24 hr) as measure collagen synthesis, well 62 5% increase total calcium 45Ca taken up indication active mineralization....

Abstract To determine whether the nonsteroidal antiestrogen tamoxifen behaves as either an agonist or antagonist of estrogen on bone, effects ovariectomy, 17β-estradiol, and were compared radial growth at tibial diaphysis in young adult female rats. Ovariectomy 17β-estradiol did not alter serum calcium, phosphate, 25-hydroxyvitamin D. increased 1,25-dihydroxyvitamin D one experiment but other. Tamoxifen calcium phosphate by itself change 1,25-dihydroxy vitamin ovariectomized produced...

Abstract The physiological role of gonadal androgens in regulating bone metabolism is not established. To determine if antagonize the changes cortical after gonadectomy, we treated orchiectomized (ORX) rats with testosterone (T) and 5α‐dihydrotestosterone (DHT), ovariectomized (OVX) afore‐mentioned androgens, as well synthetic androgen fluoxymesterone (FI) nonsteroidal estrogen diethylstilbestrol (DES). OVX resulted a rapid, sustained increase periosteal formation at tibial diaphysis,...

Bone cells respond to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) for mineral mobilization and contain receptors 1,25(OH)2D3. We report here the expression of 25-hydroxyvitamin (25 (OH)D3) metabolizing enzymes in primary cultures human bone cells, as well n a osteosarcoma cell line. Human were obtained by enzyme digestion extracellular matrix from iliac crest biopsies 3 male patients without disease. These plated (5 X 10(4)/min) medium with 10% fetal calf serum proliferated confluence 10-14 days....

A number of conditions, including osteoporosis, frailty, and sexual dysfunction in both men women have been improved using androgens. However, androgens are not widely used for these indications because the side effects associated with drugs. We describe an androgen receptor (AR) ligand that maintains expected anabolic activities substantially diminished activity prostate. LGD2226 is a nonsteroidal, nonaromatizable, highly selective AR, exhibiting virtually no affinity other intracellular...

A bstract : This review briefly assesses the well‐established effects of alcohol consumption on bone and mineral metabolism addresses areas controversy that need additional research. Alcohol is a risk factor for osteoporosis based frequent finding low mass, decreased formation rate, increased fracture incidence in alcoholics. also has been shown to reduce healthy humans animals decrease proliferation cultured osteoblastic cells. On other hand, it difficult demonstrate alcohol‐induced loss...

Glucocorticoids (GCs) are commonly used to treat inflammatory disease; unfortunately, the long-term use of these steroids leads a large number debilitating side effects. The antiinflammatory effects GCs result GC receptor (GR)-mediated inhibition expression proinflammatory genes as well GR-mediated activation genes. Similarly, most likely due both activated and repressed GR target in affected tissues. An yet unachieved pharmaceutical goal is development compound capable separating...

The effects of the nonsteroidal antiestrogen tamoxifen were determined on trabecular bone mass in proximal tibial metaphysis intact and ovariectomized rats. Rats at beginning study. On day 7 study, 5-mg slow release pellets or placebo implanted sc. All rats killed 28 experiment. Sections stained for acid phosphatase evaluated histomorphometrically. Ovariectomy resulted marked loss bone. Compared to values sham-operated animals, a sampling site secondary spongiosa was reduced by more than...

Abstract Parathyroid hormone (PTH) has biphasic effects on bone: continuous treatment is catabolic whereas intermittent anabolic. The mechanism(s) responsible for these differing are still unclear, partly because of the previous non‐availability a model system in which both formation and resorption indices could be studied concomitantly. In cultured marrow cells from 6‐week old C57BL/6 mice, we demonstrated that 4 days PTH increased mRNA osteoblast differentiation markers (Runx2, alkaline...

Bone loss occurs as a consequence of exposure to microgravity. Using the hindlimb-unloaded rat model spaceflight, this study had its purpose determine whether skeletal unloading and cephalic fluid shifts alter bone blood flow. We hypothesized that perfusion would be diminished in hindlimb bones increased structures forelimbs head. radiolabeled microspheres, we measured during control standing after 10 min, 7 days, 28 days (HU). Femoral tibial were reduced with min HU, flow femoral shaft...

Estrogen deficiency induced bone loss is associated with increased turnover in rats and humans. The respective roles of altered balance between formation resorption mediating estrogen deficiency-induced cancellous was investigated ovariectomized rats. Ovariectomy resulted the distal femur. However, preferentially lost metaphysis, a site that normally experiences low strain energy. No observed epiphysis, experiencing higher role mechanical maintaining by altering history. Mechanical decreased...

Abstract This report describes histomorphometric evidence for an important role of androgens in maintaining cancellous bone balance at a remodeling site vivo. Rats were orchiectomized (ORX) 7 weeks age and received either or vehicle 1 week later (testosterone, 1-dehydrotestosterone, 5-dihydrotestosterone) by subcutaneous pellet, producing controlled release the drug 3 weeks. Intact male rats untreated ORX animals served as controls. After 4 resulted undetectable serum testosterone levels...

Abstract The effects of castration on bone histomorphometry and mineral homeostasis were compared in male female rats. Measurements performed 4 weeks after sham operation or gonadectomy. Orchiectomy produced increases serum calcium decreases testosterone androstenedione, whereas ovariectomy estradiol testosterone. did not alter static histomorphometric measurements the tibial diaphysis, increased cross-sectional medullary areas, lowered endosteal tetracycline-labeled surface length, markedly...

Previous in vitro studies rachitic rat liver suggested that 1,25-dihydroxyvitamin D inhibits the hepatic production of 25-hydroxyvitamin (25-OHD). An investigation therefore was carried out eight normal subjects to determine whether concomitant administration D3 [1,25(OH)2D3] would alter response serum 25-OHD challenge with vitamin D. In control studies, D, 100,000 U/d for 4 d, significantly increased mean 25-OHD, from 26.3 +/- 2.9 66.7 12.6 ng/ml (P less than 0.01). contrast, 1,25(OH)2D3, 2...

Recent studies provide evidence for extrarenal production of 1 alpha ,25-dihydroxyvitamin D [1 ,25(OH)2D]. To investigate this possibility, serum vitamin D, 25-hydroxyvitamin (25-OHD), 24,25-dihydroxyvitamin [24,25(OH)2D], and ,25(OH)2D were measured in eight adult anephric subjects. All undergoing hemodialysis three them receiving 50,000 or 100,000 U/d. Serum was elevated two the patients given abnormally low others. Mean 25-OHD increased (94.0 +/- 7.6 ng/ml) normal others (16.4 0.9 ng/ml,...