Denosumab in treatment-naïve and pre-treated with zoledronic acid postmenopausal women with low bone mass: Effect on bone mineral density and bone turnover markers

Anastasilakis, Athanasios D.; Polyzos, Stergios A.; Efstathiadou, Zoe; Savvidis, M.; Sakellariou, G; Παπαθεοδώρου, Αθανάσιος; Kokkoris, Panagiotis; Makras, Polyzois

doi:10.1016/j.metabol.2015.06.018

Cited by 26 publications

(12 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As an indicator of bone mass bone mineral density (BMD) implies the bone turnover state [ 21 ]. Our results showed BMD decreased in fluoride-treated rats and it was significantly reduced in high dose of fluoride group compared to the control and low dose of fluoride groups.…”

Section: Resultsmentioning

confidence: 99%

Fluoride Regulate Osteoblastic Transforming Growth Factor-β1 Signaling by Mediating Recycling of the Type I Receptor ALK5

Yang

Wang

2017

PLoS ONE

View full text Add to dashboard Cite

This study aimed to preliminary investigate the role of activin receptor-like kinase (ALK) 5 as one of TGF-βR1 subtypes in bone turnover and osteoblastic differentiation induced by fluoride. We analyzed bone mineral density and the expression of genes related with transforming growth factor-β1(TGF-β1) signaling and bone turnover in rats treated by different concentrations of fluoride with or without SB431542 in vivo. Moreover, MTT assay, alkaline phosphatase staining, RT-PCR, immunocytochemical analysis and western blot analysis were used to detect the influence on bone marrow stem cells (BMSC) after stimulating by varying concentration of fluoride with or without SB431542 in vitro. The in vivo study showed SB431542 treatment affected bone density and gene expression of rats, which indicated TGF-β1 and ALK5 might take part in fluoride-induced bone turnover and bone formation. The in vitro study showed low concentration of fluoride improved BMSC cells viability, alkaline phosphatase activity, and osteocalcin protein expression which were inhibited by high concentration of fluoride. The gene expression of Runx2 and ALK5 in cells increased after low concentration fluoride treatment which was also inhibited by high concentration of fluoride. Fluoride treatment inhibited gene and protein expression of Samd3 (except 1 mgF-/L). Compared with fluoride treatment alone, cells differentiation was inhibited with SB431542 treatment. Moreover, the expression of Runx2, ALK5 and Smad3 were influenced by SB431542 treatment. In conclusion, this preliminary study indicated that fluoride regulated osteoblastic TGFβ1 signaling in bone turnover and cells differentiation via ALK5.

show abstract

Section: Resultsmentioning

confidence: 99%

Fluoride Regulate Osteoblastic Transforming Growth Factor-β1 Signaling by Mediating Recycling of the Type I Receptor ALK5

Yang

Wang

2017

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…RCTs investigating the efficacy of Dmab in women previously on BPs are summarized in Table 2. It is of interest that Dmab administration results in similarly suppressed BTMs, despite the lower baseline levels in patients pretreated with BPs compared to treatment-naïve patients (54,84,85). BMD increases with Dmab were similar between responders and non-responders to previous BP treatment (84).…”

Section: Transitioning From Bps To Dmabmentioning

confidence: 91%

“…The majority of patients participating in the FREEDOM trial were treatment naïve and those who were not should have been off-treatment for at least 12 months (52). In studies evaluating patients previously treated with other agents, most commonly BPs, the increases in BMD with Dmab were more modest compared to treatment-naïve patients treated with Dmab, although still significant, despite the similar reduction of BTM (30,54,55,56). Up to date, there are no data regarding the anti-fracture efficacy of Dmab in patients transitioning from other agents.…”

Section: Efficacymentioning

confidence: 99%

THERAPY OF ENDOCRINE DISEASE: Denosumab vs bisphosphonates for the treatment of postmenopausal osteoporosis

Anastasilakis

Polyzos

Makras

2018

European Journal of Endocrinology

Self Cite

101

View full text Add to dashboard Cite

The most widely used medications for the treatment of osteoporosis are currently bisphosphonates (BPs) and denosumab (Dmab). Both are antiresorptives, thus targeting the osteoclast and inhibiting bone resorption. Dmab achieves greater suppression of bone turnover and greater increases of bone mineral density (BMD) at all skeletal sites, both in naïve and pretreated patients. No superiority on fracture risk reduction has been documented so far. In long-term administration, BPs reach a plateau in BMD response after 2-3 years, especially at the hip, while BMD increases progressively for as long as Dmab is administered. Both BPs and Dmab are generally considered safe, although they have been correlated to rare adverse events, such as osteonecrosis of the jaw and atypical femoral fractures. Dmab should be preferred in patients with impaired renal function. BPs are embedded in the bone, from which they are slowly released during bone remodeling, therefore continuing to act for years after their discontinuation. In contrast, Dmab discontinuation fully and rapidly reverses its effects on bone markers and BMD and increases the risk for fractures; therefore, Dmab discontinuation should be discouraged, especially in previously treatment-naïve patients, regardless of the conventional fracture risk. In case of discontinuation, other treatment, mainly BPs, should immediately follow, although the optimal sequential treatment strategy is yet to be defined. Combination of teriparatide with Dmab or zoledronic acid, but not alendronate, provides increased BMD gains at all sites. In conclusion, both BPs and Dmab are safe and efficient therapeutic options although their particularities should be carefully considered in an individual basis.

show abstract

“…Denosumab also resulted in greater increases in BMD compared to risedronate [29] , [30] , ibandronate [30] , [31] and zoledronic acid [32] in patients who had previously received bisphosphonate therapy. Significant increases in BMD and reductions in biochemical markers of bone turnover were observed with denosumab in patients previously treated with zoledronic acid [33] . These results are in contrast to the observation that transitioning from alendronate to zoledronic acid resulted in no additional increase in BMD over 12 months [34] .…”

Section: Denosumab With or Following Other Osteoporosis Therapiesmentioning

confidence: 93%

Denosumab for the treatment of osteoporosis

McClung

2017

Osteoporosis and Sarcopenia

View full text Add to dashboard Cite

Denosumab, a specific inhibitor of RANK ligand, is a novel therapy for postmenopausal osteoporosis and related disorders. An extensive clinical development program has evaluated the clinical efficacy and safety of denosumab with several thousand patients being followed for up to 10 years. Combined with more than six years of postmarketing experience, these studies provide substantial confidence that denosumab is a convenient and appropriate treatment for patients, including Asians, at high risk for fracture. This review will summarize the clinical development of denosumab and lessons learned since its approval for clinical use in 2010.

show abstract

Denosumab in treatment-naïve and pre-treated with zoledronic acid postmenopausal women with low bone mass: Effect on bone mineral density and bone turnover markers

Cited by 26 publications

References 14 publications

Fluoride Regulate Osteoblastic Transforming Growth Factor-β1 Signaling by Mediating Recycling of the Type I Receptor ALK5

Fluoride Regulate Osteoblastic Transforming Growth Factor-β1 Signaling by Mediating Recycling of the Type I Receptor ALK5

THERAPY OF ENDOCRINE DISEASE: Denosumab vs bisphosphonates for the treatment of postmenopausal osteoporosis

Denosumab for the treatment of osteoporosis

Contact Info

Product

Resources

About