Fracture Risk and Zoledronic Acid Therapy in Men with Osteoporosis

Boonen, Steven; Reginster, Jean‐Yves; Kaufman, Jean‐Marc; Lippuner, Kurt; Zanchetta, José R.; Langdahl, Bente; Rizzoli, René; Lipschitz, Stanley; Dimai, Hans Peter; Witvrouw, Richard; Eriksen, Erik Fink; Brixen, Kim; Russo, Luís Augusto Tavares; Claessens, Frank; Papanastasiou, P.; Antunez, Oscar; Su, Guoqin; Bucci‐Rechtweg, Christina; Hruska, Josef; Incera, Elodie; Vanderschueren, Dirk; Orwoll, Eric

doi:10.1056/nejmoa1204061

Cited by 304 publications

(258 citation statements)

References 29 publications

Supporting

Mentioning

240

Contrasting

Unclassified

Order By: Relevance

“…For example, bisphosphonates and denosumab have been associated with osteonecrosis of the jaw and atypical femur fractures. In addition, bisphosphonates have been associated with atrial fibrillation and kidney damage (11,12). Therefore, the development of novel therapies for the treatment of osteoporosis is required.…”

Section: Introductionmentioning

confidence: 99%

Low-molecular weight fucoidan inhibits the differentiation of osteoclasts and reduces osteoporosis in ovariectomized rats

Jin

Zhu

et al. 2016

Molecular Medicine Reports

View full text Add to dashboard Cite

Abstract. Fucoidan is a type of sulfated polysaccharide isolated from seaweed. The present study used ovariectomized Sprague-Dawley rats, which were treated with fucoidan. The effects of fucoidan on bone metabolism, density and microarchitecture were assessed using micro-computed tomography (CT), histomorphometric analysis, biochemical markers of bone metabolism (Serum procollagen type I N propeptide and C-terminal telopeptide-1) and tests of mechanical competence of the femur. In addition, the effects of low-molecular weight fucoidan (LMWF) on in vitro cultured osteoclasts were examined, in order to determine the mechanisms underlying LMWF-induced osteoclastic inhibition. In ovariectomized rats, LMWF increased femoral bone density. Micro-CT scan also revealed that LMWF prevented microarchitectural deterioration and histomorphometric analysis determined that LMWF increased trabecular bone number and reduced the surface of bone resorption. In addition, LMWF reduced the high bone turnover rate, and improved the mechanical properties of the femur in ovariectomized rats. In vitro experiments revealed that LMWF inhibited the receptor activator of nuclear factor κB ligand (RANKL) and macrophage colony-stimulating factor-induced differentiation of RAW264.7 cells into tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts, and reduced the bone resorption surface of the osteoclasts. Reverse transcription-quantitative polymerase chain reaction demonstrated that LMWF inhibited mRNA expression of TRAP, matrix metallopeptidase-9, nuclear activator of activated T-cells 1, and osteoclast-associated immunoglobulin-like receptor, which are components of the signaling pathway for osteoclast differentiation. LMWF had no effect on RANK mRNA expression. In conclusion, the present study confirmed that LMWF inhibited osteoclast differentiation and bone resorption, and may be a potential treatment for osteoporosis in ovariectomized rats.

show abstract

Section: Introductionmentioning

confidence: 99%

Low-molecular weight fucoidan inhibits the differentiation of osteoclasts and reduces osteoporosis in ovariectomized rats

Jin

Zhu

et al. 2016

Molecular Medicine Reports

View full text Add to dashboard Cite

show abstract

“…A recent comparative study of once-yearly zoledronic acid 5 mg and once-weekly alendronate demonstrated noninferiority of zoledronic acid with regards to changes in BMD and bone turnover markers in men with osteoporosis (44). The most recently published multicentre double-blind, placebo-controlled trial of 1199 men reported fewer incident vertebral fractures with zoledronic acid (1.6% versus 4.9%, p=0.002), along with significant increases in BMD and decreases in bone turnover markers (45). Zoledronic acid use also has limitations and inconveniences: need for intravenous access and administration; monitoring of renal function, with dose adjustments and withholding to prevent renal injury in patients who develop renal impairment during treatment.…”

Section: Discussionmentioning

confidence: 99%

Denosumab is really effective in the treatment of osteoporosis secondary to hypogonadism in prostate carcinoma patients? A prospective randomized multicenter international study

Doria

Leali

Solla

et al. 2016

ccmbm

View full text Add to dashboard Cite

SummaryIntroduction. Osteoporosis is a complication of androgen deprivation therapy (ADT) in men with prostate carcinoma. The best defense against osteoporosis in prostate cancer is to identify patients with a high risk for fracture during the first clinical visit, select an effective anti-osteoporosis agent, and advise the patient to change his lifestyle and diet to prevent further bone loss. New agents include denosumab, a human monoclonal antibody that inhibits the RANK ligand (RANKL). RANKL promotes the formation, activity, and survival of osteoclasts and, thus, supports the breakdown of bone. Purpose. This is a multicenter, randomized, double-blind prospective study on use of denosumab versus alendronate in the therapy of secondary osteoporosis related to ADT in prostate cancer patients in three European countries (Italy, France, Switzerland). Patients and methods. In this 24-month observation study we enrolled 234 patients with diagnosis of osteoporosis underwent ADT for prostate cancer. All patients aged ≥55 years and had a dual-energy X-ray absorptiometry (DEXA) T-score <-1.0 (hip or spine, measured within last 2 years) and ≥ 1 fragility fracture. Patients were randomly assigned 1:1 to receive denosumab 60 mg subcutaneously every 6 months or alendronate (70 mg weekly) for 2 years. All patient received supplemental vitamin D (600 IU per day) and supplemental calcium to maintain a calcium intake of 1200 mg per day. Effectiveness of therapy in both groups (denosumab group and alendronate group) was assessed by changes in bone turnover markers (BTMs), Bone Mineral Density (BMD), fracture incidence, Visual Analogue Scale (VAS) score for back pain, and Short Form-8 (SF-8TM) health survey score for healthrelated quality of life (HRQoL). Percent changes from baseline in BTMs and BMD were assessed using the paired t test; a P-value 0.05). Mean changes in BMD at final follow-up differed significantly between two groups. BMD changes at the lumbar spine at 24 months were 5.6% with denosumab vs -1.1% with alendronate (P<0.001). New vertebral fractures developed in fewer patients in the denosumab group than in the alendronate group during the 24-month period, although this difference was not significant (P=0.10). Back pain significantly (P<0.001) improved from baseline at all time points during the study in both study groups. SF-8 health survey scores significantly improved following treatment with both drugs. Incidence of adverse drug reactions were similar in both groups. Conclusion. In our study denosumab and alendronate showed similar clinical efficacy in the therapy of ADT-related osteoporosis in men with prostate carcinoma; both drugs provided significant improvements in back pain and general health conditions. Denosumab showed significant increase of BTMs and BMD than alendronate with lower rate of new vertebral fractures.

show abstract

“…Even so, in studies in which Brazilian researchers obtain regulatory approval before the end of recruitment, the country presents excellent performance, including a significant number of patients in record time, showing the high capacity of clinical research centers in Brazil. [17][18][19] It is estimated that these 18 studies alone represent a loss of financial investment of more than 14.6 million dollars. The financial losses are even more dramatic if we take into account other countries with similar geographical, cultural or economic features as the basis for potential studies that might have been allocated to Brazil: USD 32.5 million compared to the BRIC countries and USD 24.3 million compared to Latin America.…”

Section: Discussionmentioning

confidence: 99%

Impact of regulatory assessment on clinical studies in Brazil

Russo

Eliaschewitz²,

Harada³

et al. 2016

Rev. Assoc. Med. Bras.

View full text Add to dashboard Cite

Introduction: Despite the recent expansion of clinical studies allocated to Brazil, the delay of local regulatory deadlines directly impacts their completion. Objective: This article examines the allocation process of clinical studies to Brazil in comparison with other countries, as well as the financial impact of studies not completed due to interruption caused by the delay in the regulatory process. Method: The allocation processes of studies were compared in nine countries with similar stages of economic development and countries in Latin America using the websites http://data.worldbank.org/data-catalog/GDP-rankings-table and http://worldpopulationreview.com and clinicaltrials.gov, comprising 185 countries. The 46 studies sponsored by the pharmaceutical industry underwent an analysis of the regulatory review process. Results: 46 studies sponsored by the industry and submitted in the country between June 2007 and June 2013 were analyzed; 18 (39%) were discontinued due to the delay in obtaining the necessary approvals. For the approved studies, patient recruitment began an average of 11 months after the other countries. It is estimated that 530 Brazilians patients did not have the opportunity to participate in these studies. Financial losses were to the order of 14.6 million dollars for the country, including patient, medication and supplies costs, and expenses. Conclusion: Brazil has enormous potential for the realization of clinical studies. Researchers, associations of disabled people and patients with chronic diseases, sponsors and the authorities must work together to develop an approval process that is efficient, predictable and, most of all, transparent. The current regulatory environment must and can be improved and optimized in order to result in tangible benefits for patients, society and the country's scientific development.

show abstract

Fracture Risk and Zoledronic Acid Therapy in Men with Osteoporosis

Abstract: Zoledronic acid treatment was associated with a significantly reduced risk of vertebral fracture among men with osteoporosis. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT00439647.).

Cited by 304 publications

References 29 publications

Low-molecular weight fucoidan inhibits the differentiation of osteoclasts and reduces osteoporosis in ovariectomized rats

Low-molecular weight fucoidan inhibits the differentiation of osteoclasts and reduces osteoporosis in ovariectomized rats

Denosumab is really effective in the treatment of osteoporosis secondary to hypogonadism in prostate carcinoma patients? A prospective randomized multicenter international study

Impact of regulatory assessment on clinical studies in Brazil

Contact Info

Product

Resources

About