Short-Term Prophylaxis against Estrogen Depletion-Induced Bone Loss with Calcitriol does not Provide Long-Term Beneficial Effects on Cancellous Bone Mass or Structure in Ovariectomized Rats

1998 ◽  
Vol 8 (1) ◽  
pp. 82-91 ◽  
Author(s):  
R.G. Erben ◽  
S. Bromm ◽  
M. Stangassinger
2011 ◽  
Vol 212 (2) ◽  
pp. 179-186 ◽  
Author(s):  
Rana Samadfam ◽  
Malaika Awori ◽  
Agnes Bénardeau ◽  
Frieder Bauss ◽  
Elena Sebokova ◽  
...  

Peroxisome proliferator-activated receptor (PPAR) γ agonists, such as pioglitazone (Pio), improve glycemia and lipid profile but are associated with bone loss and fracture risk. Data regarding bone effects of PPARα agonists (including fenofibrate (Feno)) are limited, although animal studies suggest that Feno may increase bone mass. This study investigated the effects of a 13-week oral combination treatment with Pio (10 mg/kg per day)+Feno (25 mg/kg per day) on body composition and bone mass parameters compared with Pio or Feno alone in adult ovariectomized (OVX) rats, with a 4-week bone depletion period, followed by a 6-week treatment-free period. Treatment of OVX rats with Pio+Feno resulted in ∼50% lower fat mass gain compared with Pio treatment alone. Combination treatment with Pio+Feno partially prevented Pio-induced loss of bone mineral content (∼45%) and bone mineral density (BMD; ∼60%) at the lumbar spine. Similar effects of treatments were observed at the femur, most notably at sites rich in trabecular bone. At the proximal tibial metaphysis, concomitant treatment with Pio+Feno prevented Pio exacerbation of ovariectomy-induced loss of trabecular bone, resulting in BMD values in the Pio+Feno group comparable to OVX controls. Discontinuation of Pio or Feno treatment of OVX rats was associated with partial reversal of effects on bone loss or bone mass gain, respectively, while values in the Pio+Feno group remained comparable to OVX controls. These data suggest that concurrent/dual agonism of PPARγ and PPARα may reduce the negative effects of PPARγ agonism on bone mass.


2015 ◽  
Vol 227 (3) ◽  
pp. 129-141 ◽  
Author(s):  
Russell T Turner ◽  
Michael Dube ◽  
Adam J Branscum ◽  
Carmen P Wong ◽  
Dawn A Olson ◽  
...  

Excessive weight gain in adults is associated with a variety of negative health outcomes. Unfortunately, dieting, exercise, and pharmacological interventions have had limited long-term success in weight control and can result in detrimental side effects, including accelerating age-related cancellous bone loss. We investigated the efficacy of using hypothalamic leptin gene therapy as an alternative method for reducing weight in skeletally-mature (9 months old) female rats and determined the impact of leptin-induced weight loss on bone mass, density, and microarchitecture, and serum biomarkers of bone turnover (CTx and osteocalcin). Rats were implanted with cannulae in the 3rd ventricle of the hypothalamus and injected with either recombinant adeno-associated virus encoding the gene for rat leptin (rAAV-Leptin,n=7) or a control vector encoding green fluorescent protein (rAAV-GFP,n=10) and sacrificed 18 weeks later. A baseline control group (n=7) was sacrificed at vector administration. rAAV-Leptin-treated rats lost weight (−4±2%) while rAAV-GFP-treated rats gained weight (14±2%) during the study. At study termination, rAAV-Leptin-treated rats weighed 17% less than rAAV-GFP-treated rats and had lower abdominal white adipose tissue weight (−80%), serum leptin (−77%), and serum IGF1 (−34%). Cancellous bone volume fraction in distal femur metaphysis and epiphysis, and in lumbar vertebra tended to be lower (P<0.1) in rAAV-GFP-treated rats (13.5 months old) compared to baseline control rats (9 months old). Significant differences in cancellous bone or biomarkers of bone turnover were not detected between rAAV-Leptin and rAAV-GFP rats. In summary, rAAV-Leptin-treated rats maintained a lower body weight compared to baseline and rAAV-GFP-treated rats with minimal effects on bone mass, density, microarchitecture, or biochemical markers of bone turnover.


2021 ◽  
Vol 22 (24) ◽  
pp. 13609
Author(s):  
Lucas Wauters ◽  
Raúl Y. Tito ◽  
Matthias Ceulemans ◽  
Maarten Lambaerts ◽  
Alison Accarie ◽  
...  

Proton pump inhibitors (PPI) may improve symptoms in functional dyspepsia (FD) through duodenal eosinophil-reducing effects. However, the contribution of the microbiome to FD symptoms and its interaction with PPI remains elusive. Aseptic duodenal brushings and biopsies were performed before and after PPI intake (4 weeks Pantoprazole 40 mg daily, FD-starters and controls) or withdrawal (2 months, FD-stoppers) for 16S-rRNA sequencing. Between- and within-group changes in genera or diversity and associations with symptoms or duodenal factors were analyzed. In total, 30 controls, 28 FD-starters and 19 FD-stoppers were followed. Mucus-associated Porphyromonas was lower in FD-starters vs. controls and correlated with symptoms in FD and duodenal eosinophils in both groups, while Streptococcus correlated with eosinophils in controls. Although clinical and eosinophil-reducing effects of PPI therapy were unrelated to microbiota changes in FD-starters, increased Streptococcus was associated with duodenal PPI effects in controls and remained higher despite withdrawal of long-term PPI therapy in FD-stoppers. Thus, duodenal microbiome analysis demonstrated differential mucus-associated genera, with a potential role of Porphyromonas in FD pathophysiology. While beneficial effects of short-term PPI therapy were not associated with microbial changes in FD-starters, increased Streptococcus and its association with PPIeffects in controls suggest a role for duodenal dysbiosis after long-term PPI therapy.


1998 ◽  
Vol 43 (3-6) ◽  
pp. 65-75 ◽  
Author(s):  
A.E. Goodship ◽  
J.L. Cunningham ◽  
V. Oganov ◽  
J. Darling ◽  
A.W. Miles ◽  
...  

1986 ◽  
Vol 110 (2) ◽  
pp. 361-366 ◽  
Author(s):  
H. F. Urbanski ◽  
S. R. Ojeda

ABSTRACT The immature female rat shows a mid-afternoon surge of prolactin secretion which reaches a maximum on the day of first pro-oestrus. The present experiments were undertaken to elucidate the mechanisms which underly the development of this prolactin discharge. Detailed plasma prolactin profiles were obtained from short-term (48 h) ovariectomized rats at 23, 28 or 37 days of age. In the two older groups, but not the youngest, a mid-afternoon surge of prolactin secretion occurred in spite of the absence of the ovaries. To exclude the possibility that such an apparent ovarian-independent discharge of prolactin was due to an oestradiol effect which persisted for 2 days following ovariectomy, another study was conducted using long-term ovariectomized animals. Plasma profiles were obtained from neonatally ovariectomized rats at ages equivalent to juvenile (26–28 days), peripubertal (38–41 days) or adult (46–49 days) phases of development. A mid-afternoon surge of prolactin secretion was observed in the majority of animals (eight out of twelve) irrespective of the interval after ovariectomy; this finding further indicates that in the female rat there is a centrally originated mid-afternoon episode of prolactin secretion which is expressed during juvenile development even in the absence of the ovaries. The relatively small magnitude of these ovarian-independent prolactin discharges (c.f. the preovulatory prolactin surge) suggested that in the intact animal they are amplified by ovarian secretions. To test this hypothesis, oestradiol-containing silicone elastomer capsules were implanted s.c. into juvenile rats, immediately after ovariectomy, and plasma prolactin profiles examined 2 days later (28 days of age). In all cases the prolactin surge was greatly amplified and in many instances the magnitude was identical to that observed at first pro-oestrus. These data suggest that development of the large pro-oestrous surge of prolactin secretion involves the interplay of at least two distinct neuroendocrine mechanisms: (1) a centrally originated ovarian-independent signal and (2) an amplification effect exerted by ovarian oestradiol. J. Endocr. (1986) 110, 361–366


2002 ◽  
Vol 55 (4) ◽  
pp. 1363-1383 ◽  
Author(s):  
Annabel S. C. Thorn ◽  
Susan E. Gathercole ◽  
Clive R. Frankish

Four experiments examined the origins of language familiarity effects in bilingual short-term recall. In Experiments 1A and 1B, bilingual adults were tested on serial recall and probed serial recall of words and nonwords in their first and second languages. A first-language advantage was obtained on both measures, indicating that the beneficial effects of language familiarity are not exclusively attributable to lesser output delay during overt recall. In Experiments 2A and 2B, the same group of bilinguals was tested on serial recall and serial recognition of word lists in both languages. Although a sizeable first-language advantage was obtained on the serial recall measure, recognition performance was comparable in the two languages. On the basis of these results it is suggested that language differences in bilingual immediate memory arise in large part as a consequence of the differential availability of language-specific long-term knowledge with which to support retrieval processes in serial recall.


Sign in / Sign up

Export Citation Format

Share Document