Deletion of the P2Y13 receptor leads to reduced bone turnover and protection from ovariectomy-induced bone loss

Bone ◽  
2011 ◽  
Vol 48 ◽  
pp. S227
Author(s):  
N. Wang ◽  
B. Robaye ◽  
A. Agrawal ◽  
G. Reilly ◽  
J.-M. Boeynaems ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Turnover

Impaired Estrogen Sensitivity in Bone by Inhibiting Both Estrogen Receptor a and b Pathways*

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Bone Mineral Density ◽  
Estrogen Receptor ◽  
Bone Loss ◽  
Bone Turnover ◽  
Bone Mineral ◽  
Female Rats ◽  
Wild Type ◽  
Mineral Density ◽  
Transgenic Rats ◽  
Estrogen Sensitivity

Although it is well established that estrogen deficiencycauses osteoporosis among the postmenopausalwomen, the involvement of estrogen receptor (ER) in itspathogenesis still remains uncertain. In the presentstudy, we have generated rats harboring a dominantnegative ERa, which inhibits the actions of not only ERabut also recently identified ERb. Contrary to our expectation,the bone mineral density (BMD) of the resultingtransgenic female rats was maintained at the same levelwith that of the wild-type littermates when sham-operated.In addition, ovariectomy-induced bone loss wasobserved almost equally in both groups. Strikingly, however,the BMD of the transgenic female rats, after ovariectomized,remained decreased even if 17b-estradiol(E2) was administrated, whereas, in contrast, the decreaseof littermate BMD was completely prevented byE2. Moreover, bone histomorphometrical analysis ofovariectomized transgenic rats revealed that the higherrates of bone turnover still remained after treatmentwith E2. These results demonstrate that the preventionfrom the ovariectomy-induced bone loss by estrogen ismediated by ER pathways and that the maintenanceof BMD before ovariectomy might be compensatedby other mechanisms distinct from ERa and ERbpathways.

scholarly journals Hypothalamic leptin gene therapy reduces body weight without accelerating age-related bone loss

2015 ◽  
Vol 227 (3) ◽  
pp. 129-141 ◽  
Author(s):  
Russell T Turner ◽  
Michael Dube ◽  
Adam J Branscum ◽  
Carmen P Wong ◽  
Dawn A Olson ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Body Weight ◽  
Bone Loss ◽  
Bone Mass ◽  
Bone Turnover ◽  
Cancellous Bone ◽  
Mass Density ◽  
Female Rats ◽  
Bone Mass Density ◽  
Age Related

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.

scholarly journals Raloxifene Has No Efficacy in Reducing the High Bone Turnover and the Risk of Spontaneous Vertebral Fractures after Denosumab Discontinuation

2018 ◽  
Vol 2018 ◽  
pp. 1-4 ◽  
Author(s):  
Elena Gonzalez-Rodriguez ◽  
Delphine Stoll ◽  
Olivier Lamy
Keyword(s):  
Bone Loss ◽  
Bone Turnover ◽  
Aromatase Inhibitors ◽  
Vertebral Fractures ◽  
Bone Markers ◽  
Rebound Effect ◽  
High Bone Turnover ◽  
Antiresorptive Agent ◽  
High Bone

At denosumab discontinuation, an antiresorptive agent is prescribed to reduce the high bone turnover, the rapid bone loss, and the risk of spontaneous vertebral fractures. We report the case of a woman treated with aromatase inhibitors and denosumab for 5 years. Raloxifene was then prescribed to prevent the rebound effect. Raloxifene was ineffective to reduce the high bone turnover and to avoid spontaneous clinical vertebral fractures. We believe that among the antiresorptive treatments, the most powerful bisphosphonates should be favored, and their administration adapted according to the serial follow-up of bone markers.

scholarly journals Bisphosphonates

2006 ◽  
Vol 50 (4) ◽  
pp. 735-744 ◽  
Author(s):  
Michael McClung
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Bone Turnover ◽  
Bone Structure ◽  
Clinical Settings ◽  
Low Bone Mass ◽  
Dosing Regimen ◽  
Drug Induced ◽  
Excellent Safety Profile ◽  
Reduce Fracture Risk

Osteoporosis is the result of bone loss due to an imbalance in bone turnover such that bone resorption exceeds bone formation. Bisphosphonates are potent inhibitors of osteoclast activity that reduce bone turnover and re-establish the balance between bone resorption and formation. In clinical studies, several bisphosphonates prevent bone loss, preserve bone structure, improve bone strength and, in patients with osteoporosis, substantially reduce fracture risk. They are effective in multiple clinical settings including postmenopausal osteoporosis, low bone mass in men and drug-induced bone loss. Intermittent oral dosing and intravenous administration are more convenient than the original daily dosing regimen. These drugs are generally well tolerated and have an excellent safety profile in that serious side effects are uncommon. Potent bisphosphonates are generally the preferred treatment option for most patients with or at risk for osteoporosis.

scholarly journals Skeletal Health After Continuation, Withdrawal, or Delay of Alendronate in Men With Prostate Cancer Undergoing Androgen-Deprivation Therapy

2008 ◽  
Vol 26 (27) ◽  
pp. 4426-4434 ◽  
Author(s):  
Susan L. Greenspan ◽  
Joel B. Nelson ◽  
Donald L. Trump ◽  
Julie M. Wagner ◽  
Megan E. Miller ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Density ◽  
Bone Loss ◽  
Bone Turnover ◽  
Androgen Deprivation Therapy ◽  
Bisphosphonate Therapy ◽  
Androgen Deprivation ◽  
Mineral Density ◽  
Skeletal Health ◽  
Oral Bisphosphonate

Purpose Androgen-deprivation therapy (ADT) for prostate cancer is associated with bone loss and osteoporotic fractures. Our objective was to examine changes in bone density and turnover with sustained, discontinued, or delayed oral bisphosphonate therapy in men receiving ADT. Patients and Methods A total of 112 men with nonmetastatic prostate cancer receiving ADT were randomly assigned to alendronate 70 mg once weekly or placebo in a double-blind, partial-crossover trial with a second random assignment at year 2 for those who initially received active therapy. Outcomes included bone mineral density and bone turnover markers. Results Men initially randomly assigned to alendronate and randomly reassigned at year 2 to continue had additional bone density gains at the spine (mean, 2.3% ± 0.7) and hip (mean, 1.3% ± 0.5%; both P < .01); those randomly assigned to placebo in year 2 maintained density at the spine and hip but lost (mean, −1.9% ± 0.6%; P < .01) at the forearm. Patients randomly assigned to begin alendronate in year 2 experienced improvements in bone mass at the spine and hip, but experienced less of an increase compared with those who initiated alendronate at baseline. Men receiving alendronate for 2 years experienced a mean 6.7% (± 1.2%) increase at the spine and a 3.2% (± 1.5%) at the hip (both P < .05). Bone turnover remained suppressed. Conclusion Among men with nonmetastatic prostate cancer receiving ADT, once-weekly alendronate improves bone density and decreases turnover. A second year of alendronate provides additional skeletal benefit, whereas discontinuation results in bone loss and increased bone turnover. Delay in bisphosphonate therapy appears detrimental to bone health.

Biochemical Markers of Bone Turnover Reflect Femoral Bone Loss in Elderly Women

1996 ◽  
Vol 59 (5) ◽  
pp. 328-333 ◽  
Author(s):  
R. Dresner-Pollak ◽  
R. A. Parker ◽  
M. Poku ◽  
J. Thompson ◽  
M. J. Seibel ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Turnover ◽  
Biochemical Markers ◽  
Elderly Women ◽  
Femoral Bone ◽  
Markers Of Bone Turnover

scholarly journals Exercise Mitigates Bone Loss in Women With Severe Obesity After Roux-en-Y Gastric Bypass: A Randomized Controlled Trial

2019 ◽  
Vol 104 (10) ◽  
pp. 4639-4650 ◽  
Author(s):  
Igor H Murai ◽  
Hamilton Roschel ◽  
Wagner S Dantas ◽  
Saulo Gil ◽  
Carlos Merege-Filho ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Bone Loss ◽  
Bone Turnover ◽  
Distal Radius ◽  
Biochemical Markers ◽  
Severe Obesity ◽  
Controlled Trial ◽  
Type I ◽  
Mineral Density ◽  
Randomized Controlled

Abstract Context Bone loss after bariatric surgery potentially could be mitigated by exercise. Objective To investigate the role of exercise training (ET) in attenuating bariatric surgery–induced bone loss. Design Randomized, controlled trial. Setting Referral center for bariatric surgery. Patients Seventy women with severe obesity, aged 25 to 55 years, who underwent Roux-en-Y gastric bypass (RYGB). Intervention Supervised, 6-month, ET program after RYGB vs. standard of care (RYGB only). Outcomes Areal bone mineral density (aBMD) was the primary outcome. Bone microarchitecture, bone turnover, and biochemical markers were secondary outcomes. Results Surgery significantly decreased femoral neck, total hip, distal radius, and whole body aBMD (P < 0.001); and increased bone turnover markers, including collagen type I C-telopeptide (CTX), procollagen type I N-propeptide (P1NP), sclerostin, and osteopontin (P < 0.05). Compared with RYGB only, exercise mitigated the percent loss of aBMD at femoral neck [estimated mean difference (EMD), −2.91%; P = 0.007;], total hip (EMD, −2.26%; P = 0.009), distal radius (EMD, −1.87%; P = 0.038), and cortical volumetric bone mineral density at distal radius (EMD, −2.09%; P = 0.024). Exercise also attenuated CTX (EMD, −0.20 ng/mL; P = 0.002), P1NP (EMD, −17.59 ng/mL; P = 0.024), and sclerostin levels (EMD, −610 pg/mL; P = 0.046) in comparison with RYGB. Exercise did not affect biochemical markers (e.g., 25(OH)D, calcium, intact PTH, phosphorus, and magnesium). Conclusion Exercise mitigated bariatric surgery–induced bone loss, possibly through mechanisms involving suppression in bone turnover and sclerostin. Exercise should be incorporated in postsurgery care to preserve bone mass.

scholarly journals The Short-Term Effects of Prunes in Preventing Inflammation and Improving Indices of Bone Health in Osteopenic Men

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 5-5
Author(s):  
Bahram Arjmandi ◽  
Kelli George ◽  
Lauren Ormsbee ◽  
Neda Akhavan ◽  
Joseph Munoz ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Bone Loss ◽  
Bone Turnover ◽  
Systolic Blood Pressure ◽  
Dietary Intervention ◽  
Male Rats ◽  
Health Concern ◽  
Control Group ◽  
Daily Consumption ◽  
Significant Group

Abstract Objectives Osteoporosis is a public health concern for both women and men. Chronic inflammation contributes to bone loss; therefore, foods rich in antioxidants, such as prunes, are of great interest. Previously, dietary intervention with prunes has been shown to prevent orchidectomy-induced decreases in BMD, microstructure, and biomechanics in male rats; however, there is a need for this to be studied in a clinical setting in adult males. Methods Thirty-five men between the ages of 55 and 80 with moderate bone loss were included. The men were randomized into one of three groups: 100 g prunes daily, 50 g prunes daily, or control group. All three groups also consumed a multivitamin containing 450 mg calcium and 800 IU vitamin D. Serum samples from the baseline and three-month time points were analyzed for biomarkers of bone turnover, inflammation, and oxidative stress. Results After three months, daily consumption of 100 g prunes was associated with a significant decrease in serum concentrations of osteocalcin (P &lt; 0.001). Consumption of 50 g of prunes was associated with significant decreases in systolic blood pressure, and serum osteocalcin concentrations (P = 0.040), and an increase in the OPG: RANKL ratio (P = 0.041). There were also significant decreases in systolic blood pressure, OPG (P = 0.004), RANKL (P = 0.010), and osteocalcin (P = 0.049) in control group. There was a significant group*time effect for changes in OPG (P = 0.019) and the OPG: RANKL ratio (P = 0.029). Conclusions Decreases in osteocalcin indicate a decrease in bone turnover, and a higher OPG: RANKL ratio indicates that more RANKL is bound to OPG, and not to osteoclasts, thus downregulating osteoclast activity. Therefore, regular consumption of either 100 g or 50 g dried plum for three months may make some contributions to bone formation and bone turnover activity, and minimal contribution to decreasing inflammation and improving bone density and quality. Funding Sources USDA/NIFA, California Prune Board, and Shaklee.

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