ASB4 modulates central melanocortinergic neurons and calcitonin signaling to control satiety and glucose homeostasis.

Variants in the gene encoding ankyrin repeat and SOCS box-containing 4 (ASB4) are linked to human obesity. Here, we characterized the pathways underlying the metabolic functions of ASB4. Hypothalamic Asb4 expression was suppressed by fasting in wild-type mice but not in mice deficient in AgRP, which encodes Agouti-related protein (AgRP), an appetite-stimulating hormone, suggesting that ASB4 is a negative target of AgRP. Many ASB4 neurons in the brain were adjacent to AgRP terminals, and feeding induced by AgRP neuronal activation was disrupted in Asb4-deficient mice. Acute knockdown of Asb4 in the brain caused marked hyperphagia due to increased meal size, and Asb4 deficiency led to increased meal size and food intake at the onset of refeeding, when very large meals were consumed. Asb4-deficient mice were resistant to the meal-terminating effects of exogenously administered calcitonin and showed decreased neuronal expression of Calcr, which encodes the calcitonin receptor. Pro-opiomelanocortin (POMC) neurons in the arcuate nucleus in mice are involved in glucose homeostasis, and Asb4 deficiency specifically in POMC neurons resulted in glucose intolerance that was independent of obesity. Furthermore, individuals with type 2 diabetes showed reduced ASB4 abundance in the infundibular nuclei, the human equivalent of the arcuate nucleus. Together, our results indicate that ASB4 acts in the brain to improve glucose homeostasis and to induce satiety after substantial meals, particularly those after food deprivation.

Association between vitamin D deficiency and exercise capacity in patients with CKD, a cross-sectional analysis.

BACKGROUND: Evidence is growing for a role of vitamin D in regulating skeletal muscle mass, strength and functional capacity. Given the role the kidneys play in activating total vitamin D, and the high prevalence of vitamin D deficiency in Chronic Kidney Disease (CKD), it is possible that deficiency contributes to the low levels of physical function and muscle mass in these patients. METHODS: This is a secondary cross-sectional analysis of previously published interventional study, with in vitro follow up work. 34 CKD patients at stages G3b-5 (eGFR 25.5 ± 8.3 mL/min/1.73m2; age 61 ± 12 years) were recruited, with a sub-group (n = 20) also donating a muscle biopsy. Vitamin D and associated metabolites were analysed in plasma by liquid chromatography tandem-mass spectroscopy and correlated to a range of physiological tests of muscle size, function, exercise capacity and body composition. The effects of 1α,25(OH)2D3 supplementation on myogenesis and myotube size was investigated in primary skeletal muscle cells from vitamin D deficient donors. RESULTS: In vivo, there was no association between total or active vitamin D and muscle size or strength, but a significant correlation with V̇O2Peak was seen with total vitamin D (25OHD). in vitro, 1α,25(OH)2D3 supplementation reduced IL-6 mRNA expression, but had no effect upon proliferation, differentiation or myotube diameter. CONCLUSIONS: Vitamin D deficiency is not a prominent factor driving the loss of muscle mass in CKD, but may play a role in reduced exercise capacity.

Synergistic and non-synergistic effects of salmon calcitonin and omega - 3 fatty acids on antioxidant, anti-inflammatory, and haematological indices in diabetic rats.

The optimum therapy for the management of diabetes mellitus (DM) has been a controversial issue. Therefore, the study investigated the effects of salmon calcitonin (Sct) and/or omega-3 fatty acids {eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA); EPA/DHA ratio?=?3/2} relative to metformin in diabetic male Wistar rats. Forty rats were used for this study. They were randomly divided into 8 groups of five (5) rats each, which were treated with single or combined administration of salmon calcitonin, N-3 and metformin. DM was induced by the administration of streptozotocin (65?mg/kg b.w., i.p.), 15?min after the administration of nicotinamide (110?mg/kg b.w., i.p.). Nine days afterwards, treatments started, and they lasted for 28 days. Sct was administered at 2.5 and 5.0 IU/kg b.w./day (i.m.), while, N-3 and metformin were administered at 200 and 180?mg/kg b.w./day (p.o.) respectively. The results showed that the induced DM significantly increased pro-inflammatory markers, and significantly altered antioxidant and haematological indices. The combined administration of Sct and N-3 had synergistic effects on total bilirubin and total antioxidant capacity, but, non-synergistic actions on malondialdehyde, uric acid, interleukin-6, lactate dehydrogenase, superoxide dismutase, catalase, glutathione peroxidase, and the haematological parameters. These effects were comparable to that of metformin which showed a more or less therapeutic action than N-3. The study concluded that the antioxidant, anti-inflammatory, and haematological effects of the combined administration of Sct and N-3 is comparable to that of metformin. Nevertheless, the latter showed more or less therapeutic effects relative to N-3.

Local administration of calcitonin inhibits alveolar bone loss in an experimental periodontitis in rats.

Calcitonin (CTN), a calcium regulatory hormone, promotes calcium diuresis from the kidney and suppresses bone resorption. The objective of this study was to evaluate whether the topical and intermittent application of CTN inhibits alveolar bone resorption using ligature-induced experimental periodontitis in rats. Experimental periodontitis was induced by placing a nylon ligature around maxillary molars of 8-week-old male Wistar rats for 20 days. Thirty-two rats were divided into four groups: basal sham control group, periodontitis group, periodontitis plus 0.2 U CTN (low dose), and periodontitis plus 1.0 U CTN (high dose) group. To investigate the effects of CTN on alveolar bone resorption, CTN was topically injected into the palatal gingivae every 2 days after ligature removal (day 0). Micro-computed tomography (CT) analysis was performed for linear parameter assessment of alveolar bone on day 5 and day 14. Periodontal tissues were examined histo-pathologically to assess the differences among the study groups. Micro-CT images showed that alveolar bone resorption was induced statistically around the molar of ligatured rats on day 5 and day 14. The amount of bone resorption was more severe on day 14 than that on day 5. On day 5, only high-dose CTN treatment significantly suppressed bone resorption. In addition, both doses of CTN significantly suppressed bone resorption on day 14. Histological examination clarified that there were fewer TRAP-positive cells in the CTN treatment groups than in the periodontitis group on day 5. Local administration of CTN decreased alveolar bone resorption by regulating osteoclast activation in rats with periodontitis.

Effects of Salmon Calcitonin and Omega - 3 Fatty Acids on Glucoregulatory Indices, Lipid Profile and Antioxidant Markers in Experimental Knee Osteoarthritis in Wistar Rats.

It has been opined that a combined therapeutic approach should be considered in the optimal management ofosteoarthritis (OA). Therefore, the study investigated the effects of salmon calcitonin (Sct) and/or omega-3 fatty acids (N-3), relative to diclofenac sodium (DF) on selected biochemical parameters in induced osteoarthritic rats. Forty (40) adultmale Wistar rats were used for this study. The rats were divided into 8 groups (n=5), viz: Group 1-Normal control; Group 2-OA control; Group 3-OA+N-3 (200 mg/kg, p.o.); Group 4-OA + low dose of Sct (Sct.Lw-2.5 IU/kg, i.m.); Group 5-OA +high dose of SCT (Sct.Hi-5.0 IU/kg, i.m.); Group 6-OA+N-3+Sct.Lw; Group 7-OA+N-3+Sct.Hi; and, Group 8-OA+DF (1mg/kg, p.o.). Osteoarthritis was induced with 4 mg of sodium monoiodoacetate in 40 µl of saline. The solution was injectedintra-articularly into the left knee joint space of anaesthetised (sodium pentobarbital - 40 mg/kg, i.p.) rats. Nine (9) daysafterwards, treatments started, and they lasted for 28 days. The results showed that Sct has hypocalcaemic, hypocortisolism,and anti-dyslipidaemic effects. It significantly inhibited nitric oxide (NO) production and insulin release. Like Sct, N-3 havehypocortisolism and anti-dyslipidaemic actions. Nevertheless, they caused significant increases in hepatic glycogen contentand plasma levels of calcium ion, insulin and NO. Although DF was also observed to stimulate insulin release and NOsynthesis, it significantly increased plasma level of LDL-c, but significantly decreased HDL-C. In conclusion, N-3 annul theundesirable effect of Sct, presenting it as a better anti-arthritic drug. Moreover, the combined administration of bothpharmacological agents proffer preferable therapeutic benefits in OA condition relative the single or DF therapy.

Reduced glutathione biosynthesis in Drosophila melanogaster causes neuronal defects linked to copper deficiency.

Glutathione (GSH) is a tripeptide often considered to be the master antioxidant in cells. GSH plays an integral role in cellular redox regulation and is also known to have a role in mammalian copper homeostasis. In vitro evidence suggests that GSH is involved in copper uptake, sequestration and efflux. This study was undertaken to further investigate the roles that GSH plays in neuronal copper homeostasis in vivo, using the model organism Drosophila melanogaster. RNA interference-mediated knockdown of the Glutamate-cysteine ligase catalytic subunit gene (Gclc) that encodes the rate-limiting enzyme in GSH biosynthesis was utilised to genetically deplete GSH levels. When Gclc was knocked down in all neurons, this caused lethality, which was partially rescued by copper supplementation and was exacerbated by additional knockdown of the copper uptake transporter Ctr1A, or over-expression of the copper efflux transporter ATP7. Furthermore, when Gclc was knocked down in a subset of neuropeptide-producing cells, this resulted in adult progeny with unexpanded wings, a phenotype previously associated with copper dyshomeostasis. In these cells, Gclc suppression caused a decrease in axon branching, a phenotype further enhanced by ATP7 over-expression. Therefore, we conclude that GSH may play an important role in regulating neuronal copper levels and that reduction in GSH may lead to functional copper deficiency in neurons in vivo. We provide genetic evidence that glutathione (GSH) levels influence Cu content or distribution in vivo, in Drosophila neurons. GSH could be required for binding Cu imported by Ctr1A and distributing it to chaperones, such as Mtn, CCS and Atox1. Alternatively, GSH could modify the copper-binding and transport activities of Atox1 and the ATP7 efflux protein via glutathionylation of copper-binding cysteines.

Calcium supplements: benefits and risks.

Calcium is an essential element in the diet, but there is continuing controversy regarding its optimal intake, and its role in the pathogenesis of osteoporosis. Most studies show little evidence of a relationship between calcium intake and bone density, or the rate of bone loss. Re-analysis of data from the placebo group from the Auckland Calcium Study demonstrates no relationship between dietary calcium intake and rate of bone loss over 5 years in healthy older women with intakes varying from <400 to >1500 mg day(-1) . Thus, supplements are not needed within this range of intakes to compensate for a demonstrable dietary deficiency, but might be acting as weak anti-resorptive agents via effects on parathyroid hormone and calcitonin. Consistent with this, supplements do acutely reduce bone resorption and produce small short-term effects on bone density, without evidence of a cumulative density benefit. As a result, anti-fracture efficacy remains unproven, with no evidence to support hip fracture prevention (other than in a cohort with severe vitamin D deficiency) and total fracture numbers are reduced by 0-10%, depending on which meta-analysis is considered. Five recent large studies have failed to demonstrate fracture prevention in their primary analyses. This must be balanced against an increase in gastrointestinal side effects (including a doubling of hospital admissions for these problems), a 17% increase in renal calculi and a 20-40% increase in risk of myocardial infarction. Each of these adverse events alone neutralizes any possible benefit in fracture prevention. Thus, calcium supplements appear to have a negative risk-benefit effect, and so should not be used routinely in the prevention or treatment of osteoporosis.

Central administration of aminoprocalcitonin inhibits food intake and stimulates the hypothalamic-pituitary-adrenal axis in rats via the corticotrophin-releasing factor system.

Aminoprocalcitonin (N-PCT), a neuroendocrine peptide derived from procalcitonin, reduces food intake and body weight when administered centrally in rats. We have recently shown that N-PCT is expressed in brain areas known to be involved in energy homeostasis, including the paraventricular nucleus (PVN) of the hypothalamus, which contains a prominent population of corticotrophin-releasing factor (CRF)-synthesising neurones. CRF plays a pivotal role in the regulation of the hypothalamic-pituitary adrenal (HPA) axis and food intake. However, little is known about functional interactions of N-PCT and CRF. In the present study, we found endogenous N-PCT protein in the rat PVN. We also showed N-PCT immunoreactivity in PVN co-localised with NeuN, a neuronal marker, or glial fibrillary acidic protein, an astrocyte marker. Double staining immunohistochemistry revealed that N-PCT co-localised with CRF in parvocellular neurones of the PVN. Intracerebroventricular N-PCT administration increased CRF mRNA and content in the hypothalamus, suggesting that N-PCT stimulates the HPA axis and suppresses food intake and body weight via CRF-dependent pathways. In keeping with this, i.c.v. co-injection of D-Phe-CRF(12-41), a CRF receptor antagonist, significantly attenuated N-PCT-induced reduction in food intake and body weight in a dose-dependent manner. Furthermore, i.c.v. administration of N-PCT increased plasma adrenocorticotrophic hormone and corticosterone concentrations and induced the expression of Fos protein, a marker of neuronal activity, in parvocellular CRF neurones. These data collectively support the hypothesis that N-PCT inhibits food intake and body weight and stimulates the HPA axis via CRF-mediated pathways.

Comparison of the effects of alendronate sodium and calcitonin on bone-prosthesis osseointegration in osteoporotic rats.

UNLABELLED: Alendronate (ALO) and calcitonin (CT), as commonly used antiosteoporosis drugs in current clinical practice, have been experimentally confirmed to produce the effectiveness of promoting osseointegration at the interface between prosthesis and host bone and enhancing the long-term stability of the prosthesis. Our current study compared these two drugs' effects on the osseointegration of prosthesis and found that both of them could promote bone attachment between prosthesis and host bone; moreover, ALO produced more pronounced effectiveness. INTRODUCTION: A series of findings confirmed that ALO and CT improved bone attachment of implant in animals. However, which one shows stronger effectiveness has not yet been reported by previous researches. Our study compared the effects of the two commonly used antiosteoporosis drugs on the bone-prosthesis osseointegration so as to provide valuable reference for current clinical options of medication. METHODS: Forty female SD rats aged 5 months were randomly set into A, B, C, and D groups. Except for group A, the others were ovariectomized to establish osteoporosis model (lumbar bone mineral density (BMD) decreased by 20% 4 weeks after ovariectomy). All the rats received prosthesis implantation at their tibial plateau. Then, the rats in groups C and D were given ALO (7 mg/kg/w) orally and CT (5 IU/kg/day) subcutaneously for 12 weeks, respectively. Prior to the execution, application of tetracycline hydrochloride for staining in vivo was done. After harvesting and embedding, the tibia with implants were cut into thin slides, then the bone histomorphometry was measured to observe the new bone around prosthesis and to calculate the osseointegration rate of the implants. By comparison, the effect of the two drugs on osseointegration was evaluated. RESULTS: (1) Both ALO and CT can effectively enhance the volume of bone mass surrounding the hydroxyapatite (HA) prosthesis and also significantly lever up osseointegration rate to 63.7% and 45.7%, respectively (p < 0.05). However, ALO produced more periprosthesis osseointegration rate than CT, with difference of 18% (p < 0.05). (2) The rats' lumber BMD increased in both ALO and CT groups, from 0.081 ± 0.009 and 0.078 ± 0.009 to 0.116 ± 0.008 and 0.109 ± 0.010 g/cm(2), respectively. Moreover, the effect of ALO was observed more pronounced than that of CT. CONCLUSIONS: In osteoporotic conditions, both administration of ALO orally and CT subcutaneously can enhance periprosthesis bone mass and the effects on osseointegration between host bone and prosthesis. Compared with CT, the effect of ALO is more pronounced.

The relevance of preclinical research models for the development of antimigraine drugs: focus on 5-HT(1B/1D) and CGRP receptors.

Migraine is a complex neurovascular syndrome, causing a unilateral pulsating headache with accompanying symptoms. The past four decades have contributed immensely to our present understanding of migraine pathophysiology and have led to the introduction of specific antimigraine therapies, much to the relief of migraineurs. Pathophysiological factors culminating into migraine headaches have not yet been completely deciphered and, thus, pose an additional challenge for preclinical research in the absence of any direct experimental marker. Migraine provocation experiments in humans use a head-score to evaluate migraine, as articulated by the volunteer, which cannot be applied to laboratory animals. Therefore, basic research focuses on different symptoms and putative mechanisms, one at a time or in combination, to validate the hypotheses. Studies in several species, utilizing different preclinical approaches, have significantly contributed to the two antimigraine principles in therapeutics, namely: 5-HT(1B/1D) receptor agonists (known as triptans) and CGRP receptor antagonists (known as gepants). This review will analyze the preclinical experimental models currently known for the development of these therapeutic principles, which are mainly based on the vascular and/or neurogenic theories of migraine pathogenesis. These include models based on the involvement of cranial vasodilatation and/or the trigeminovascular system in migraine. Clearly, the preclinical strategies should involve both approaches, while incorporating the newer ideas/techniques in order to get better insights into migraine pathophysiology.

Immunoneutralization of the aminoprocalcitonin peptide of procalcitonin protects rats from lethal endotoxaemia: neuroendocrine and systemic studies.

Severe sepsis and septic shock are an important cause of mortality and morbidity. These illnesses can be triggered by the bacterial endotoxin LPS (lipopolysaccharide) and pro-inflammatory cytokines, particularly TNF-α (tumour necrosis factor-α) and IL (interleukin)-1ß. Severity and mortality of sepsis have also been associated with high concentrations of N-PCT (aminoprocalcitonin), a 57-amino-acid neuroendocrine peptide derived from ProCT (procalcitonin). Previous studies in a lethal model of porcine polymicrobial sepsis have revealed that immunoneutralization with IgG that is reactive to porcine N-PCT significantly improves short-term survival. To explore further the pathophysiological role of N-PCT in sepsis, we developed an antibody raised against a highly conserved amino acid sequence of human N-PCT [N-PCT-(44-57)]. This sequence differs by only one amino acid from rat N-PCT. First, we demonstrated the specificity of this antibody in a well-proven model of anorexia induced in rats by central administration of human N-PCT-(1-57). Next we explored further the therapeutic potential of anti-N-PCT-(44-57) in a rat model of lethal endotoxaemia and determined how this immunoneutralization affected LPS-induced lethality and cytokine production. We show that this specific antibody inhibited the LPS-induced early release of TNF-α and IL-1ß and increased survival, even if treatment began after the cytokine response had occurred. In addition, anti-N-PCT-(44-57) may increase long-term survival in LPS-treated rats by up-regulating the late production of counter-regulatory anti-inflammatory mediators such as ACTH (adrenocorticotropic hormone) and IL-10. In conclusion, these results support N-PCT as a pro-inflammatory factor in both the early and the late stages of lethal endotoxaemia, and suggest anti-N-PCT as a candidate for septic shock therapy.

Effect of low-level laser therapy and calcitonin on bone repair in castrated rats: a densitometric study.

OBJECTIVE: To investigate the healing of bone defects in male rats treated with salmon calcitonin, low-level laser therapy (LLLT), or both. BACKGROUND: Healing of bone defects still represents a challenge to health professionals in several areas. In this article, the effect of calcitonin in combination with LLLT on bone repair was studied. Densitometry was used as a valuable tool for the measurement of bone regeneration. METHODS: Sixty male Wistar rats underwent bilateral castration surgery before the creation of a surgical bone defect. The animals were randomly divided into four groups: control, treated with calcitonin (Ca), treated with LLLT (La), and treated with calcitonin and LLLT (CaLa). Groups Ca and CaLa received 2 IU/kg of synthetic salmon calcitonin intramuscularly three times a week. Groups La and CaLa received laser therapy using a gallium-aluminum-arsenide laser (10 mW, 20 J/cm(2), wavelength 830 nm). Control animals were submitted to sham irradiation. The animals were sacrificed 7, 14, and 21 days after surgery, and bone defects were analyzed using densitometry. RESULTS: The CaLa group had a higher degree of bone regeneration 14 and 21 days after surgery. CONCLUSIONS: The La and CaLa had significantly higher bone mineral density than the control and Ca groups.

Homeopathic treatment for bone regeneration: experimental study.

AIM AND METHOD: The objective of this research was to study the effect of homeopathic treatment with Plumbum metallicum (Plumbum met.) on mandibular bone repair in rats. MATERIALS AND METHODS: We analyzed the mandibles of 60 male rats, approximately 3-month-old, randomly divided into three groups of 20 animals each: control, treated with calcitonin, and treated with a homeopathic medicine. A circumscribed bone defect measuring 4mm in diameter was made in the mandible and covered with a polytetrafluorethylene (PTFE) barrier. The group treated with calcitonin received 2IU/kg intramuscularly three times a week; the group treated with Plumbum met. 30c received three drops in water every day. The animals were sacrificed after 7, 14, 21 and 28 days. The mandibles were removed and submitted to histologic and histomorphometric analyses. RESULTS: Data were analyzed statistically by two-way ANOVA and by the Tukey test. The interaction effect (ANOVA, F df(6; 48)=4.64; p=0.001<0.05) indicated that the relationship between treatments was not the same at each time of sacrifice. Although statistical analysis of the histomorphometric data showed a similar results for the treated and control groups. But histological analysis showed complete filling of the surgical defect throughout its extent was only for the group treated with Plumbum met. CONCLUSION: The study demonstrated that for repair of surgical defects in rat mandibles Plumbum met. 30c and control did not differ significantly in histomorphometric terms.

Central calcitonin exerts anorectic effects via the hypothalamus in chicks.

Calcitonin (CT) causes satiety in mammals, but the mechanisms that mediate this effect are poorly understood. Additionally, there are no reports on CT-induced satiety within the avian class. Therefore, the purpose of this study was to elucidate some of the central mechanisms regulating CT-induced satiety in a non-mammalian vertebrate, the chick. Broiler-type chicks, at 4 days of age, responded to central CT (0.3, 1.0 and 3.0 nmol) with both reduced food and water intake. The effect on water intake was secondary to that of food. An increased number of c-Fos immunoreactive cells were found in hypothalamic nuclei associated with satiety including the arcuate nucleus, dorsomedial nucleus and ventromedial hypothalamus after central CT injection. Increased jumps, distance traveled and time spent perching on food containers were also observed, and these behaviors are likely not competitive with ingestion. Also, central CT injection was associated with reduced food pecks, but increased pecking efficiency. Blockage of corticotrophin releasing factor receptors did not prevent central CT-induced satiety. Central CT appears to be a regulator of satiety in chicks and this effect is likely mediated via interactions within the hypothalamus.

Procalcitonin N-terminal peptide causes catabolic effects via the hypothalamus and prostaglandin-dependent pathways.

Recent evidence suggests that the free amino-terminal fragment of procalcitonin (N-PCT) plays a role in the central control of feeding behavior and energy homeostasis. However, little is known about the mechanisms through which N-PCT works. Here we report that intracerebroventricular administration of N-PCT to free-feeding male rats induced a significant decrease of longer-term food intake and body weight gain. Conversely, N-PCT increased body temperature. We also show that intracerebroventricular administration of N-PCT induced a marked neuronal activation in key thermoregulatory and feeding areas of the hypothalamus. We further show that N-PCT increases the responsiveness of proopiomelanocortin anorexigenic neurons in the arcuate nucleus of the hypothalamus, and that stimulation of the de novo synthesis of prostaglandins is crucial for the central effects induced by N-PCT. Results support the role of N-PCT to the central control of feeding behavior and suggest that N-PCT, acting probably through the eicosanoid cyclooxygenase pathway, may act as a signaling molecule in the hypothalamus by regulating the activity of anorexigenic neurons in the hypothalamus.

Improved intestinal absorption of calcitonin by mucoadhesive delivery of novel pectin-liposome nanocomplexes.

Self-assembling pectin-liposome nanocomplexes (PLNs) were prepared by a simple mixing of cationic liposomes with pectin solution, in order to improve intestinal absorption of calcitonin (eCT). Both in-vitro and in-vivo evaluations for PLNs were evaluated. The results showed that average particle size of PLNs was significantly larger than that of initial cationic liposomes. The surface charges were shifted from positive to negative after mixing with pectin. The PLNs made of high degree of esterification (DE) pectin showed less negatively charged values than those made of low DE pectin. The entrapment efficiency in cationic liposomes was in the same range even if the drug loading was increased. The in-vivo mucoadhesive test of pectin by confocal laser scanning microscopy demonstrated stronger mucoadhesive properties of PLNs made of low DE pectin, compared to cationic liposomes and PLNs made of other pectins. Moreover, high intensities of a fluorescent marker could be observed throughout the small intestines (i.e. duodenum, jejunum and ileum) and remained at the site of mucoadhesion even after 6 h of administration of PLNs made of low DE pectin. The eCT-loaded PLNs demonstrated a strong pharmacological action over the eCT solution and eCT-loaded liposomes, in which an enhanced and prolonged reduction in plasma calcium concentration of rats was observed. This was attributed to the ability of pectin to adhere to the mucus layer and prolong retention in the intestinal mucosa.

A comparison of teriparatide and calcitonin therapy in postmenopausal Asian women with osteoporosis: a 6-month study.

OBJECTIVE: The number of hip fractures is expected to double in the next 20 years, with current estimates that Asia will account for 37% of these cases. As bone mineral density (BMD) may be used as a measure of fracture risk, we sought to compare the effects of teriparatide with salmon calcitonin treatment on changes in BMD, biochemical bone markers, and safety in postmenopausal Asian women with osteoporosis. METHODOLOGY: A total of 104 patients (n = 47 teriparatide [20 g/day subcutaneously] and n = 57 calcitonin [100 IU/day subcutaneously]) were enrolled in Hong Kong, Singapore, Philippines, Malaysia, and Thailand. Calcium (> or = 500 mg/day) and vitamin D (200-400 IU/day) supplements were taken throughout the 6-month controlled, randomized study. RESULTS: Teriparatide was associated with a 5.03 +/- 4.77% increase in lumbar spine BMD (p < 0.0001, mean +/- SD change from baseline), whereas changes in lumbar spine BMD for patients on calcitonin were not statistically significant (mean change of 0.36 +/- 4.12%, p = 0.16). Comparison of the two groups indicated that teriparatide treatment improved lumbar spine BMD statistically significantly more than calcitonin (p < 0.0001). No statistically significant changes were observed for total hip or femoral neck BMD. Serum bone-specific alkaline phosphatase (BSAP) increased by 55.9% (median change from baseline, p < 0.0001) in the teriparatide group, and remained stable with calcitonin (5.0% change, p = 0.24); osteocalcin increased by 156.15% (median change from baseline, p < 0.0001) with teriparatide, and decreased with calcitonin (-15.25%, p = 0.03). Similar rates of adverse events were observed, with nausea and dizziness the most commonly reported for both groups (teriparatide versus calcitonin, 13.0% versus 23.2% p = 0.21, 10.9% versus 21.4% p = 0.19, respectively). There were no clinically relevant changes observed in laboratory parameters. CONCLUSIONS: Both treatments were similarly tolerated, however teriparatide was associated with greater increases in lumbar spine BMD and bone formation markers, demonstrating the unique mechanism of action and safety of this treatment for osteoporosis in these Asian women.

The effect of calcitonin on biochemical markers and zinc excretion in postmenopausal osteoporosis.

OBJECTIVES: A double-blind, randomized, placebo-controlled trial was conducted in women with postmenopausal osteoporosis to evaluate effects on biochemical markers and urinary excretion of zinc (Zn) of calcitonin therapy. METHODS: Patients were required to have a bone mineral density (BMD) of 2.5 S.D. or more below the young adult mean either at the postero-anterior lumbar spine or at the femoral neck. Subjects were eligible for our study if they were 50 years or older, with at least 5 years of menopause, and in good general health as determined by medical history and a routine clinical blood analysis. The patients were randomly assigned to receive intranasal salmon calcitonin (200 IU/day; 50 patients) or placebo (50 patients). All patients received supplemental calcium (1000 mg/day). Additionally, 40 age-matched, demographically similar, healthy postmenopausal women were also selected as controls. Measurements of cross-linked N-telopeptides of type I collagen (uNTx), osteocalcin (sOC), and urinary zinc concentration were done. All parameters were measured before therapy and again after 1, 3 and 6 months. RESULTS: After 3 and 6 months of treatment, a higher decrease of most indices was observed in the calcitonin group. A statistically significant decrease occurred in the levels of sOC, uNTx and uZn after 3 and 6 months in patients receiving calcitonin therapy (P<0.05). Levels of sOC and uNTx in calcitonin group were significantly different after 3 and 6 months from both placebo and baseline values of calcitonin group (P<0.05). Levels of sOC, uNTx and uZn decreased about 40, 46 and 37%, respectively, in calcitonin group at 6 months after the start of treatment. CONCLUSIONS: Our study suggests that values of uNTx, uZn and sOC were significantly lower in the patient group than those in control group and in postmenopausal women with osteopororsis, calcitonin reduces the concentrations of uNTx, uZn and sOC.

The treatment of osteoporosis in patients with rheumatoid arthritis receiving glucocorticoids: a comparison of alendronate and intranasal salmon calcitonin.

OBJECTIVE: The purpose of this study was to assess the effects of alendronate and intranasal salmon calcitonin (sCT) treatments on bone mineral density and bone turnover in postmenopausal osteoporotic women with rheumatoid arthritis (RA) receiving low-dose glucocorticoids. METHODS: Fifty osteoporotic postmenopausal women with RA, who had been treated with low-dose corticosteroids for at least 6 months, were randomized to receive alendronate 10 mg/day or sCT 200 IU/day for a period of 24 months. All patients received calcium supplementation 1,000 mg and vitamin D 400 IU daily. Bone mineral density (BMD) of the lumbar spine, femoral neck, and trochanter was measured annually using dual-energy X-ray absorptiometry. Bone metabolism measurements included urinary deoxypyridinoline (DPD), serum bone alkaline phosphatase (BAP), and serum osteocalcin (OC). RESULTS: Over 2 years, the lumbar spine (4.34%, P < 0.001), femoral neck (2.52%, P < 0.05), and trochanteric (1.29%, P < 0.05) BMD in the alendronate group increased significantly. The sCT treatment increased lumbar spine BMD (1.75%, P < 0.05), whereas a significant bone loss occurred at the femoral neck at month 24 (-3.76%, P < 0.01). A nonsignificant decrease in the trochanteric region was observed in the sCT group (-0.81%). The difference between the groups with respect to the femoral neck and trochanteric BMD was statistically significant ( P < 0.001 and P < 0.05, respectively). The decreases in urinary DPD (-21.87%, P < 0.001), serum BAP (-10.60%, P < 0.01), and OC (-19.59%, P < 0.05) values were statistically significant in the alendronate group, whereas nonsignificant decreases were observed in the sCT group (-5.77%, -1.96%, and -4.31%, respectively). A significant difference was found in the DPD and BAP levels between the two treatment groups in favor of the alendronate group at all time points ( P = 0.001 and P < 0.05, respectively). CONCLUSION: The results of this study demonstrated that alendronate treatment produced significantly greater increases in the femoral neck BMD and greater decreases in bone turnover than intranasal sCT in RA patients receiving low dose glucocorticoids.