Ten Years of Very Infrequent Zoledronate Therapy in Older Women: An Open-Label Extension of a Randomized Trial

2020 ◽  
Vol 105 (4) ◽  
pp. e1641-e1647 ◽  
Author(s):  
Andrew Grey ◽  
Anne Horne ◽  
Greg Gamble ◽  
Borislav Mihov ◽  
Ian R Reid ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Turnover ◽  
Fracture Risk ◽  
Older Women ◽  
Academic Research ◽  
Mineral Density ◽  
Open Label ◽  
Original Cohort ◽  
Optimal Dosing ◽  
Open Label Extension

Abstract Context Intravenous zoledronate prevents bone loss and reduces fracture risk in older adults but the optimal dosing strategy required to achieve each outcome is not known. Objective To assess the effect of very infrequent zoledronate therapy on bone mineral density (BMD) and markers of bone turnover. Design and participants An average of 5.5 years after randomization to either a single dose of 5 mg of zoledronateor placebo, 33 of the original cohort of 50 older women with osteopenia entered a 5-year open-label extension study. Setting Academic research center Intervention A 5-mg dose of intravenous zoledronate was administered to all participants. Main outcome measures BMD and bone turnover were measured annually, generating data over almost 11 years in women who received 5 mg of zoledronate at 0 and 5.5 years (ZZ, n = 16), or placebo at baseline and 5 mg of zoledronate at 5.5 years (PZ, n = 17). Results After redosing, BMD in ZZ remained stable, while BMD in PZ increased. At 11 years, changes from baseline BMD in ZZ and PZ were 3.8% (95% confidence interval (CI) 1.1,6.5) and 2.9% (0.3,5.5) at the lumbar spine (P = .61), 0.9% (–1.7,3.5) and –2.8% (–5.3,–0.3) at the total hip (P = .006), and 0.4% (–0.8,1.6) and –0.4% (–1.3,0.5) at the total body (P = .14). Bone turnover markers were similar in the PZ and ZZ groups throughout the 5 years after redosing. Conclusions These results suggest that zoledronate 5 mg administered at a 5.5-year interval prevents bone loss over almost 11 years. Clinical trials to investigate whether very infrequent treatment with zoledronate reduces fracture risk are justified.

Use of age and BMD to predict fracture risk in men on androgen deprivation therapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9517-9517
Author(s):  
D. Lin ◽  
M. R. Smith ◽  
R. A. Morton ◽  
M. S. Steiner
Keyword(s):  
Prostate Cancer ◽  
Bone Mineral Density ◽  
Bone Loss ◽  
Bone Turnover ◽  
Fracture Risk ◽  
Bone Turnover Markers ◽  
Mineral Density ◽  
History Of ◽  
Baseline Characteristics ◽  
Turnover Markers

9517 Background: Androgen deprivation therapy (ADT) decreases bone mineral density by reducing estrogens to castrate levels and, as a result, increases fracture risk. We recently completed a two-year trial in 1382 men in which we examined the ability of toremifene to reduce fracture risk in men on ADT. Herein we describe analyses of the placebo group to assess the baseline characteristics associated with new fractures. Methods: We conducted a randomized double blind placebo controlled trial in 1382 men with histologically confirmed prostate cancer on ADT. Entry criteria included age ≥ 50 years, continous ADT for 6 months or longer or intermittent ADT for 12 months or longer. Subjects on intermittent ADT at enrollment had to remain on continuous ADT for their duration on study. Subjects were randomized to receive either 80mg toremifene citrate daily or matching placebo. The primary end point was the incidence of new morphometric vertebral fractures. Secondary endpoints included bone mineral density, clinical fragility fractures, bone turnover markers, lipid profile, hot flashes, and gynecomastia. Results: The modified intent to treat (MITT) population included subjects who took study medication and had an on-study radiograph. There were 467 subjects in the placebo MITT population. To identify factors associated with fracture risk in men on ADT we compared placebo subjects who suffered a fracture or during the first year on study suffered 7% or greater bone loss with those placebo subjects who did not. Baseline characteristics included: BMD (spine, hip, femoral neck), Age, history of fracture, ADT duration, bone turnover markers, and race. Logistic regression models of the probability of fracture/bone loss as a function of country showed that each of BMD at all sites, age, race, CTX, and history of previous fracture independently predicted fracture/7% bone loss. When all characteristics were analyzed in a multivariable model lower spine BMD (p=0.006) and older age (p=0.018) were significantly associated with incident fractures. Conclusions: In prostate cancer patients on ADT older age and lower baseline spine BMD were associated with a greater risk of fracture in untreated patients. [Table: see text]

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 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.

scholarly journals Effects of obesity treatments on bone mineral density, bone turnover and fracture risk in adults with overweight or obesity

2016 ◽  
Vol 28 (3) ◽  
Author(s):  
Claudia Harper ◽  
Andrea L. Pattinson ◽  
Hamish A. Fernando ◽  
Jessica Zibellini ◽  
Radhika V. Seimon ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bariatric Surgery ◽  
Weight Loss ◽  
Bone Turnover ◽  
Fracture Risk ◽  
Bone Mineral ◽  
Dietary Restriction ◽  
Mineral Density ◽  
Pre Treatment ◽  
Obesity Treatments

AbstractBackground:New evidence suggests that obesity is deleterious for bone health, and obesity treatments could potentially exacerbate this.Materials and methods:This narrative review, largely based on recent systematic reviews and meta-analyses, synthesizes the effects on bone of bariatric surgery, weight loss pharmaceuticals and dietary restriction.Results and conclusions:All three obesity treatments result in statistically significant reductions in hip bone mineral density (BMD) and increases in bone turnover relative to pre-treatment values, with the reductions in hip BMD being strongest for bariatric surgery, notably Roux-en Y gastric bypass (RYGB, 8%–11% of pre-surgical values) and weakest for dietary restriction (1%–1.5% of pre-treatment values). Weight loss pharmaceuticals (orlistat or the glucagon-like peptide-1 receptor agonist, liraglutide) induced no greater changes from pre-treatment values than control, despite greater weight loss. There is suggestive evidence that liraglutide may increase bone mineral content (BMC) – but not BMD – and reduce fracture risk, but more research is required to clarify this. All three obesity treatments have variable effects on spine BMD, probably due to greater measurement error at this site in obesity, suggesting that future research in this field could focus on hip rather than spine BMD. Various mechanisms have been proposed for BMD loss with obesity treatments, notably reduced nutritional intake/absorption and insufficient exercise, and these are potential avenues for protection against bone loss. However, a pressing outstanding question is whether this BMD reduction contributes to increased fracture risk, as has been observed after RYGB, and whether any such increase in fracture risk outweighs the risks of staying obese (unlikely).

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 Association of the G-174C Variant in the Interleukin-6 Promoter Region With Bone Loss and Fracture Risk in Older Women

2004 ◽  
Vol 19 (10) ◽  
pp. 1612-1618 ◽  
Author(s):  
Susan P Moffett ◽  
Joseph M Zmuda ◽  
Jane A Cauley ◽  
Katie L Stone ◽  
Michael C Nevitt ◽  
...  
Keyword(s):  
Bone Loss ◽  
Fracture Risk ◽  
Older Women ◽  
Interleukin 6 ◽  
Promoter Region

scholarly journals Biomarkers of bone health and osteoporosis risk

2008 ◽  
Vol 67 (2) ◽  
pp. 157-162 ◽  
Author(s):  
Richard Eastell ◽  
Rosemary A. Hannon
Keyword(s):  
Bone Turnover ◽  
Fracture Risk ◽  
Risk Reduction ◽  
Hormone Replacement ◽  
Osteoporosis Treatment ◽  
Bone Alkaline Phosphatase ◽  
Type I ◽  
Mineral Density ◽  
Markers Of Bone Turnover ◽  
Fracture Risk Reduction

The assay features of biochemical markers of bone turnover have markedly improved in the past few years. The most sensitive and specific markers of bone formation include serum bone alkaline phosphatase, total osteocalcin (including the intact molecule and the large N-mid fragment) and the procollagen type I N-terminal propeptide assay. Among the various markers of bone resorption, measurements of the urinary excretion of N- and C-terminal cross-linked telopeptides) and of serum C-terminal cross-linked telopeptides are the most sensitive and specific. Markers of bone turnover can be used to predict the rate of bone loss in post-menopausal women and can also be used to assess the risk of fractures. In osteoporosis-treatment studies (with alendronate, risedronate, raloxifene) markers of bone turnover appear even more strongly associated with fracture risk reduction than bone mineral density (BMD). These observations support the use of markers of bone turnover as surrogates for fracture risk reduction, perhaps even more so than BMD. Bone markers can also be used to monitor the efficacy of antiresorptive therapy such as hormone-replacement therapy, raloxifene and bisphosphonates in individual patients. Furthermore, they have also proved to be helpful in monitoring the response to nutritional interventions and have the advantage over BMD in that they provide information about mechanism of effect and changes are often observed much more rapidly.

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