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At least 19 recordsLinked to original sources
PubMed1984

Studies of marginal zinc deprivation in rhesus monkeys. V. Fetal and infant skeletal effects.

Skeletal maturation was evaluated in newborn and infant rhesus monkeys that had been subjected to a marginally zinc-deficient diet (4 ppm zinc) from conception through 12 months of postnatal life. Serial radiographic assessment of skeletal development was performed and compared to both ad libitum and pair-fed controls. Radiographs were obtained at birth and at 1, 3, 9, and 12 months of age. In each age group a maturation indicator was selected to identify individuals with abnormal skeletal maturation defined on the basis of presence of epiphyseal ossification centers. Animals were compared only within a given sex group. Additionally, to evaluate endochondral bone mineralization, the appearance of the zone of provisional calcification on the metaphyseal side of the growth plate and the width of the growth plate were assessed. A marginal level of zinc deprivation during gestation and during the 1st yr of life was found to be associated with significantly delayed skeletal maturation and defective mineralization. This abnormality of bone mineralization has many features similar to human rachitic syndromes and suggests that zinc plays an important role in endochondral bone formation.

Animals↗
PubMed1995

An in-vivo model for the rapid assessment of skeletal effects of anabolic agents.

We recently developed an in vivo model which can be used to rapidly assess the local skeletal effects of anabolic agents. In this model, 160 g Sprague-Dawley (SD) rats were used. A stainless steel cannula was inserted into the marrow cavity of the proximal tibia through the anterior-medial cortex 6 mm distal to the knee joint. The outer opening of the cannula was covered by skin. Agents with known anabolic skeletal effects or vehicle were injected daily for 10 days into the marrow region by a small needle passing through the cannula. Rats were also injected subcutaneously with a fluorescent bone marker to label the newly formed bone. Injection sites were fixed, embedded, and sectioned for histomorphometric analysis of trabecular bone. PTH and PGE2 stimulated a large amount of new trabecular bone formation in regions proximal and distal to the injection site as measured by histomorphometry. Control groups showed minimal bone formation, limited to formation of a thin layer of bony shell immediately surrounding the cannula. The profound anabolic skeletal effects of PTH and PGE2 seen in this Local Injection Model are similar to those seen in systemic injection (i.e. subcutaneous injection in intact or castrated male and female rats) previously reported. This Local Injection Model combines numerous advantages of in vivo models (systemic injection) and in vitro models when assessing agents with anabolic skeletal activities. Compared to conventional in vivo systemic injection models, this model enables detection of anabolic skeletal effects using very small quantities (in microgram) of test agents in a short treatment period (< 10 days).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2005

Skeletal effects in class II treatment with the functional mandibular advancer (FMA)?

OBJECTIVE: The aim of this clinical study was to reveal skeletal effects during the treatment of Class II malocclusions in adolescents and young adults using a protrusive-acting fixed, rigid functional orthodontic appliance, and to quantify them in comparison with an untreated control group. We aimed to determine whether, and if so, to what extent skeletal effects diminish with increasing age, and whether inter-individual differences can be observed. METHOD: To correct their intermaxillary jaw relationship, the functional mandibular advancer (FMA) was inserted in 16 adolescents and young adults (eight males, eight females, aged from 12 years, 3 months to 18 years, 7 months) presenting with a skeletal Class II malocclusion. The course of treatment was documented cephalometrically. RESULTS: In all patients, the FMA treatment led to neutroclusion or overcorrected neutroclusion and a marked reduction in overjet. The occlusion's improvement in the sagittal dimension (overjet reduction by 4.43 +/- 2.10 mm, molar relationship improvement by 3.88 +/- 1.12 mm) was achieved by a combination of dental effects (distalization of upper teeth, mesialization of lower teeth) and skeletal effects (mandibular growth stimulation). Excepting the position and morphology of the maxillary base and the condyle's dorsal position in the fossa, all sagittal skeletal and dental changes induced by the FMA treatment were statistically significant. There was a mean increase of 1.71 +/- 1.11 mm in sagittal length of the mandible, in the sagittal-diagonal dimension of 1.42 +/- 1.51 mm and 1.53 +/- 2.15 mm, as well as a slight, significant increase in the gonial angle area. Whereas the condylar position remained stable, a forward positioning of the chin and thus significant increase in distance length was recorded from the posterior condylar margin to the anterior mandibular margin. CONCLUSIONS: Treatment with a fixed functional appliance in Class II patients effected significant changes in mandibular growth and correction of the distal intermaxillary relationship even after the pubertal growth spurt in adolescents and young adults. While the proportion of the orthopedically-induced skeletal share is subject to substantial inter-individual variability in adolescents, the overall conclusion can be drawn that skeletal effects (= stimulation of mandibular growth) in general clearly lessen with increasing patient age. In young adult patients, the correction of a distal intermaxillary jaw relationship is manifested primarily as a dento-alveolar compensation for the skeletal malocclusion.

Adolescent↗
PubMed2003

Skeletal effects of cyclosporin A are gender related in rats.

The immunosuppressive drug cyclosporin A (CsA) is thought to be involved in the pathogenesis of posttransplantation osteoporosis. To evaluate further the skeletal effects of CsA, we treated aged male and female sham-operated and gonadectomized rats with low doses of CsA for 4 months. Here, we show that CsA is antiresorptive and bone-sparing in aged female rats but increases bone resorption and reduces bone mass in aged male rats. However, even in male rats, CsA treatment, at clinically relevant doses, increased bone resorption only transiently and did not result in pronounced long-term cancellous bone loss. The gender-specific skeletal effects of CsA were not modulated by sex hormones or gonadectomy. CsA did not influence sex steroid metabolism in male or female rats. However, endogenous estradiol in sham-operated female rats (and especially, exogenous administration of 17beta-estradiol in ovariectomized rats) markedly diminished blood levels of CsA, probably by increasing hepatic CsA metabolism. Although the mechanism for the gender-specific skeletal effects of CsA is still obscure, our findings may have important implications for clinical therapy with CsA.

Amino Acids↗
PubMedDate not supplied

Skeletal effects of statins.

OBJECTIVE: To review the skeletal effects of hydroxy-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) and evaluate the use and potential benefit of statins in the management of osteoporosis. METHODS: Background information on the topic of the effect of statins on bone and fracture risk is presented, and the pertinent published literature is reviewed. RESULTS: Osteoporosis is the most common bone disease, affecting millions of people worldwide and leading to considerable morbidity, especially when it is not adequately managed. Although statins have primarily been known for their lipid-lowering effects, recent data have documented a potential association between statin use and improvement in fracture risk profile. Some statins have been shown to decrease bone-specific alkaline phosphatase or serum osteocalcin concentrations, but other studies have failed to demonstrate the beneficial effects of these agents. Therefore, additional studies should be undertaken to clarify the mechanism of action. CONCLUSION: Observational studies suggest an association between HMG-CoA reductase inhibitors and reduction in fracture risk. Large randomized controlled clinical trials must be performed to confirm this association.

Bone Remodeling↗
PubMed1996

A comparison of the skeletal effects of intermittent and continuous administration of calcitonin in ovariectomized rats.

The study was designed to compare the skeletal effects of intermittent and continuous administration of calcitonin (CT) in ovariectomized (OVX) rats. Female rats were sham operated or OVX at 3 months of age and treated for 6 weeks with vehicle or salmon CT. Sham-operated control rats were injected subcutaneously with vehicle on alternate days. One group of OVX rats was treated with vehicle intermittently by subcutaneous injection or continuously via Alzet osmotic minipumps. The remaining OVX rats were treated with CT by either subcutaneous injections (16 U/kg) on alternate days or by continuous infusion via minipumps at a daily dose of 8 U/kg. OVX rats treated with CT continuously were mildly hypocalcemic compared with all other groups. The proximal tibial metaphyses of vehicle-treated OVX rats were osteopenic with a cancellous bone volume at only 28% of the vehicle-treated control level. This bone loss was associated with increased indices of bone turnover such as osteoclast surface, osteoblast surface, and bone formation rate. Cancellous bone volume in OVX rats treated with CT either intermittently or continuously was significantly higher than that of vehicle-treated OVX rats, but lower than that of vehicle-treated control rats. Treatment of OVX rats with intermittent or continuous CT significantly decreased all indices of bone turnover compared with vehicle-treated OVX rats. However, osteoclast and osteoblast surfaces of OVX rats treated with CT continuously were still significantly higher than those of vehicle-treated control rats. These results indicate that intermittent and continuous administration of CT had similar skeletal effects in OVX rats. Both treatment regimens depressed bone turnover and partially prevented cancellous bone loss in the estrogen-deplete skeleton.

Analysis of Variance↗
PubMedDate not supplied

Metabolic and skeletal effects of low and high doses of calcium acetate in patients with preterminal chronic renal failure.

BACKGROUND: Secondary hyperparathyroidism commonly evolves, as the glomerular filtration rate falls. The metabolic and skeletal effects of a possible remedy, calcium acetate, have not been studied in patients with preterminal chronic renal failure. METHODS: Men with a mean creatinine clearance of approximately 30 ml/min took calcium acetate for 24 weeks at doses which provided 507 or 1,521 mg calcium/day with meals. Metabolic determinations were made at intervals of 4-8 weeks, and the bone mineral density (BMD) was measured at the beginning and at the end of the trial. RESULTS: The low-dose regimen produced no metabolic or skeletal effect. In subjects prescribed the high-dose regimen, the 24-hour urine phosphorus excretion fell from 0.53 mg/mg creatinine to values ranging from 0.34 to 0.41 mg/mg creatinine. The theoretical phosphorus threshold concentration rose by a maximum of 38.6%, and the serum phosphorus concentration did not change. The mean serum calcium concentration rose by a maximum of 7.2%. The mean fractional changes in parathyroid hormone and 1,25-dihydroxyvitamin D concentrations ranged from -27.0 to -39.6% and from -5.0 to -20.3%, respectively. The BMD increased at L1, L3, and L4. CONCLUSION: Calcium acetate prescribed to deliver 1,521 mg calcium/day with meals reduced parathyroid hormone and 1,25-dihydroxyvitamin D concentrations and increased lumbar BMD in men with preterminal chronic renal failure.

Acetates↗
PubMed2006

Comparison of the skeletal effects of the progestogens desogestrel and levonorgestrel in oral contraceptive preparations in young women: controlled, open, partly randomized investigation over 13 cycles.

AIM: This 12-month study was conducted to evaluate the skeletal effects of two monophasic oral contraceptives containing 20 mug of ethinylestradiol and 100 mug of levonorgestrel (LEVO) or 150 mug of desogestrel (DESO). METHODS: Fifty-two women (18-24 years) were randomized into the DESO group or the LEVO group; 36 women served as controls. The areal bone mineral density (aBMD) of the femoral neck and the lumbar spine was evaluated by DXA, and parameters of bone geometry and volumetric bone mineral density (vBMD) were assessed by peripheral quantitative computed tomography at the distal radius and the tibia. RESULTS: The LEVO group did not lose vertebral aBMD, whereas women in the DESO group lost 1.5%. At the distal radius and the tibia (shank level, 14%), LEVO induced an increase in total cross-sectional area, indicating increased periosteal bone formation. Radial trabecular vBMD declined by 1.4+/-1.8% in the DESO group, while it remained unchanged in the LEVO group. CONCLUSION: Our study suggests that the skeletal effects of OC preparations may be influenced by progestogenic components in young women.

Absorptiometry, Photon↗
PubMed2005

Neural regulation of bone and the skeletal effects of serotonin (5-hydroxytryptamine).

There is increasing evidence for a contribution of the neural system to the regulation of bone metabolism. The skeleton is richly innervated by both sympathetic and sensory neurons. While these nerves serve sensory and vascular functions, they are also being found to influence bone cell activities. The most convincing evidence for this has been provided by studies into the skeletal effects of the hormone leptin, which has been shown to centrally regulate bone mass, and through studies into the skeletal effects of hypothalamic neuropeptide Y2 and Y4 receptors. This paper discusses recent evidence for the neural regulation of bone metabolism and, in particular, the potential role of the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). Recent studies have demonstrated the presence of functional pathways in bone for both responding to and regulating the uptake of 5-HT. This is of high clinical relevance given the role of the serotonergic system in affective disorders, and the wide use of pharmacological agents that target the 5-HT system to manage these disorders. Initial data suggest that exposure to these agents at different stages during the lifespan may have significant effects on the skeleton.

Bone and Bones↗
PubMed1997

Skeletal effects of menstrual disturbances in athletes.

This article reviews the skeletal effects and clinical implications of menstrual disturbances in active women. At the lumbar spine, menstrual disturbances are associated with premature bone loss or failure to reach peak bone mass, while appendicular sites are less affected. This suggests that trabecular bone is more sensitive to hormonal stimuli and less responsive to mechanical loading than cortical bone. Although the mechanisms responsible for the detrimental effects of menstrual disturbances are likely to be multifactorial, low circulating levels of oestrogen are thought to be the main cause. The clinical significance of menstrual disturbances depends upon a number of factors, including type of sport, genetic background, body composition and calcium intake. Not all athletes who present with menstrual disturbances will develop osteopenia. Nevertheless, the risk of stress fracture does seem to be increased in athletes with menstrual disturbances and with lower bone density. Whether athletes with menstrual disturbances are at a greater risk for osteoporosis in later life is not yet known. Bone loss can be at least partially reversed, especially with the spontaneous resumption of menses. This may serve to offset any previous increased risk of osteoporosis. Furthermore, other factors, apart from low bone mass, act to determine the likelihood of osteoporotic fractures. Therefore, the clinical significance of menstrual disturbances associated with exercise participation needs to be established for each individual athlete. Bone densitometry may guide the clinician in this respect and assist in the formulation of appropriate management strategies.

Bone Density↗
PubMed1979

Skeletal effects of megavoltage irradiation in survivors of Wilms' tumor.

The skeletal effects of megavoltage irradiation (60Co) in 25 long term survivors of Wilms' tumor are described. In general, the changes seen with megavoltage irradiation are as frequent but not as severe as those previously reported after orthovoltage irradiation. Vertebral body changes generally occur within 5 years after irradiation. Scoliosis and/or kyphosis do not usually develop until after five years postirradiation. Kyphotic curves tend to progress after the adolescent growth spurt while scoliotic curves do not. Other bony and nonosseous changes are detailed.

Bone and Bones↗
PubMed1996

Ovarian status influences the skeletal effects of tamoxifen in adult rats.

Tamoxifen (TAM), an antiestrogen used in adjuvant therapy for breast cancer, is currently being evaluated for prevention of breast cancer in premenopausal and postmenopausal disease-free women. In light of this clinical application in young women, the skeleton's potential predisposition for osteoporosis following long-term treatment with an antiestrogen is a concern. In postmenopausal women being treated for breast cancer TAM was shown to prevent bone loss. There is little information, however, about the skeletal effects of TAM in premenopausal women. Previous animal studies in ovariectomized (OVX'd) rats have consistently reported TAM to prevent cancellous and cortical bone loss. The effects of TAM on ovary-intact animals, however, are not well established. We have performed a histomorphometric analysis in order to evaluate the influence of ovarian function on the skeletal effects of long-term TAM treatment in the laboratory animal model. Six-month-old rats were implanted subcutaneously with pellets designed for the controlled release of TAM at a dose (5 mg/3 wks) previously shown to be effective at antagonizing short-term bone loss in OVX'd growing rats. TAM acted as an estrogen agonist on cortical bone measurements in tibia of ovary-intact as well as OVX'd rats. In cancellous bone of OVX'd rats, TAM reduced indices of bone formation and resorption and reduced the bone loss from over 90 percent to less than 50 percent. In ovary-intact rats, however, TAM produced a 31 percent loss of cancellous bone, a deficit associated with a 26 percent reduction in the trabecular number. These results clearly demonstrate an interaction between TAM and ovarian status whereby TAM partially prevents estrogen-deficient bone loss in OVX'd animals but antagonizes selective actions of estrogen on the skeleton of ovary-intact animals.

Analysis of Variance↗
PubMed1989

A comparison of the skeletal effects of goserelin and danazol in premenopausal women with endometriosis.

The skeletal effects of two therapies for endometriosis that produce hypo-oestrogenism in 23 premenopausal women have been studied. Eleven women received goserelin 3.6 mg monthly by subcutaneous implant and 12 women received danazol 600 mg daily, orally, both for 6 months. Goserelin causes a small decline in spinal bone density, but a greater loss of density in the proximal femur. Preliminary results show no evidence that bone loss is reversible after stopping therapy. Danazol treatment is not associated with loss of bone. Prolonged or repeated courses of treatment with goserelin alone could lead to a clinically significant adverse effect on the skeleton.

Adult↗
PubMed2001

Skeletal effects of androgen withdrawal.

Hypogonadism is considered to be one of the major risk factors for osteoporosis in men. Therefore, it is an important goal for skeletal research to improve our understanding of the skeletal effects of androgens. Androgen deficiency during growth is associated with a failure to acquire normal peak bone mass, and there is good evidence that the effects of androgens on skeletal growth and the development of a male skeletal phenotype are mediated through the androgen receptor. In adult men, acute withdrawal of androgens by surgical or chemical castration induces high turnover bone loss. Similarly, orchidectomy of aged, non-growing male rats is associated with a pronounced and sustained increase in bone turnover and with true loss of cancellous and cortical bone. Interestingly, the changes in bone turnover induced by orchidectomy are paralleled by a concomitant increase in B lymphopoiesis in bone marrow of rats and mice. Although there is firm evidence that male bone metabolism can be influenced by androgens and estrogen, a variety of clinical and animal experimental data have strongly suggested that, under physiological circumstances, the maintenance of cancellous bone mass in males involves the skeletal action of estrogen derived from aromatization of androgens. Aged male rats appear to closely mimic the conditions induced by androgen withdrawal in adult humans, and this animal model may be used 1) to elucidate further the role of muscle as a mediator of the actions of androgens on bone, 2) to explore the regulatory functions of androgens and estrogens in the male skeleton and the immune system, and 3) to find new treatment strategies for the prevention and treatment of osteoporosis in men.

Journal Article↗
PubMed1998

Skeletal effects of constant and terminated use of sodium risedronate in ovariectomized rats.

AIM: To study the skeletal effects of constant and terminated use of sodium risedronate (Ris) treatment in the ovariectomized (Ova) rats. METHODS: Ris 5 micrograms.kg-1, s.c., twice a wk. The proximal tibial metaphysis (PTM) were processed undecalcified for quantitive bone histomorphometry. RESULTS: (1) Placebo-treated (normal saline) Ova rats were characterized by decreased trabecular area (TA) on d 60, d 81, and d 150 compared with aging controls, and bone resorption was over formation with high bone turnover. (2) Ova rats were treated with Ris for 60, 81, and 150 d (Ris-on) increased. (TA 217%, 108%, and 101%) respectively, vs Ova rats and depressed bone turnover indices to aging control level, but bone mass did not maintain at high level in 150-d group as in the early stage. (3) Ova rats were pretreated with Ris for 60 d and then terminated (Ris-on/off), followed by sequential sacrifice of rats on 21 and 90 d. Withdrawal on 21 d showed the same results as the match-age Ris-on group. Withdrawal on 90 d still maintained cancellous bone mass at a high level vs 150 d Ris-on groups (+26%) and aging control group (+27%). CONCLUSION: Regimen of Ris 60 d on then 90 d off prevented the development of osteoporosis in Ova rats.

Animals↗
PubMed1999

Skeletal effects of constant and terminated use of risedronate on cortical bone in ovariectomized rats.

To study the skeletal effects of continual and terminated use of risedronate treatment on cortical bone in ovariectomized (Ovx) rats, we used risedronate (Ris), 5 microg x kg(-1), by subcutaneous injections, twice per week. The middle part of the tibial shafts (Tx) were processed undecalcified for quantitive bone histomorphometry. Cortical bone and the marrow areas of the tibial shaft did not change in either sham-Ovx or Ovx rats during the 150-day experimental period. Continued administration of Ris for 150 days decreased the marrow area and increased the percentage of cortical area compared with the matching sham and Ovx group. A decrease in bone formation indices in both periosteal and endocortical surfaces of Tx in sham-operated rats between the age of 5 and 8 months was seen. Ovariectomy increased the percentage of labeled perimeter in the periosteal area, and markedly increased the percentage of eroded perimeter in the endocortical surface compared with sham control groups in 81 and 150 days. Bone formation indices of Ris treatment were increased in periosteal surfaces, and percentages of eroded perimeter were decreased more in endocortical surfaces in 150 days than in the matching sham and Ovx groups. These data matched our static data, which showed a significantly increased percentage of cortical bone area and decreased percentage of marrow area. These bone gains were not maintained in the 90-day Ris withdrawal group. For cancellous bone, the 60-day Ris-treated high bone mass was maintained in the withdrawal group and not maintained in Ris continmuously treated group. These results indicate the effects of constant and terminated use of Ris in cortical bone were different from those in trabecular bone in the proximal tibial metaphysis.

Animals↗
PubMed1991

Skeletal effects of calcitonin in ovariectomized rats.

Although calcitonin (CT) has been shown to be effective for the prevention of bone loss in early postmenopausal women, the skeletal effects of the hormone specifically during the early stages of estrogen deficiency have not been characterized histomorphometrically to date. The current study involves use of the ovariectomized (OVX) rat as an animal model for early postmenopausal bone loss to perform such a histomorphometric analysis. One group of OVX rats was injected sc with salmon CT on alternate days for a 6-week period. Additional groups of OVX and sham-operated control rats were treated with vehicle alone. In comparison to control rats, the proximal tibia of vehicle-treated OVX rats were characterized by a 3-fold decrease in cancellous bone volume and significant increases in osteoblast surface (+200%), osteoclast surface (+143%), mineralizing surface (+111%), mineral apposition rate (+36%), bone formation rate (+181%), and longitudinal bone growth (+38%). In contrast, treatment of OVX rats with CT normalized tibial cancellous bone volume and significantly decreased all of the above cellular- and fluorochrome-based indices of bone turnover to near control levels. The results indicate that CT treatment depresses bone turnover and prevents the development of osteopenia in OVX rats. These findings are consistent with the bone protective effect of CT in early postmenopausal women and further support the OVX rat as an animal model for the preclinical evaluation of prophylactic treatments for postmenopausal bone loss.

Animals↗
PubMed1993

Skeletal effects of withdrawal of estrogen and diphosphonate treatment in ovariectomized rats.

The study was designed to determine the skeletal effects of withdrawal of estrogen and diphosphonate treatment in the estrogen-deplete state. Groups of ovariectomized (OVX) rats were treated with vehicle alone, estrogen, or the diphosphonates etidronate or risedronate for a 180-day period. A group of sham-operated control rats was treated for 180 days with vehicle alone. All treatments were then terminated, followed by sequential sacrifice of rats at 0, 35, 90, 180, and 360 days after withdrawal of treatment. The proximal tibia from each animal was processed undecalcified for quantitative bone histomorphometry. At the end of the treatment period, vehicle-treated OVX rats were characterized by cancellous osteopenia and increased bone turnover relative to vehicle-treated control rats. Treatment of OVX rats with estrogen or diphosphonates depressed bone turnover and protected against cancellous osteopenia. During the withdrawal period, OVX rats previously treated with estrogen exhibited rapid bone loss associated with increased bone turnover. The bone protective effect of the hormone in OVX rats was nearly completely lost by 90 days of withdrawal. In contrast, OVX rats maintained low levels of bone turnover and normal cancellous bone mass at 180 days of withdrawal from diphosphonate treatment. The results suggest that estrogen-deplete women who are withdrawn from estrogen replacement are at high risk for subsequent bone loss. They further suggest that widely spaced periods of intermittent diphosphonate treatment may be sufficient to prevent the development of osteopenia in postmenopausal and oophorectomized women.

Animals↗