Denosumab in Osteoporosis and Oncology

2009 ◽  
Vol 43 (9) ◽  
pp. 1445-1455 ◽  
Author(s):  
Jill S Burkiewicz ◽  
Sarah L Scarpace ◽  
Susan P Bruce
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Adverse Effects ◽  
Bone Turnover ◽  
Bone Turnover Markers ◽  
Neoplastic Disease ◽  
Mineral Density ◽  
Treatment Of Osteoporosis ◽  
Additional Clinical Trial ◽  
Turnover Markers

Objective: To review the pharmacology, pharmacokinetics, pharmacodynamics, safety, efficacy, and use of denosumab in osteoporosis, breast cancer, prostate cancer, and multiple myeloma. Data Sources: Studies and abstracts were identified through MEDLINE and International Pharmaceutical Abstracts (1966–July 2009). Key search terms include denosumab, AMG-162, and receptor activator of nuclear factor-κB ligand system. Information available in abstract form was retrieved from major oncology and bone metabolism meetings. Additional data were obtained from the manufacturer. Study Selection and Data Extraction: All available studies in humans were included except for studies in rheumatoid arthritis and giant cell tumor of the bone. Data Synthesis: In patients with osteoporosis, denosumab significantly reduces bone resorption and fractures. Studies of denosumab in the prevention and treatment of osteoporosis have demonstrated significantly increased bone mineral density and reduced bone turnover markers. Studies of denosumab versus placebo in the treatment of osteoporosis have demonstrated reductions in vertebral, hip, and nonvertebral fractures. In oncology, positive results from clinical trials in patients receiving endocrine therapy for breast and prostate cancer demonstrated decreases in bone loss and skeletal-related events. Denosumab seems to be at least as effective in reducing bone turnover markers as intravenous bisphosphonates in the oncology setting. The most common adverse effects in patients with osteoporosis were arthralgia, nasopharyngitis, back pain, and headache. The most common adverse effects in patients with cancer were infection, pain in the extremities, arthralgia, bone pain, fatigue, and pain. Serious adverse effects include infections requiring hospitalization. Conclusions: Denosumab has documented efficacy and safety in patients with osteoporosis, breast cancer, and prostate cancer. Additional clinical trial data are needed to more completely establish the effectiveness of denosumab in the treatment of osteoporosis and neoplastic disease as well as its cost-effectiveness and long-term safety.

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]

Vitamin D3 analogs for the treatment of osteoporosis

2015 ◽  
Vol 93 (5) ◽  
pp. 327-332 ◽  
Author(s):  
Hiroshi Hagino
Keyword(s):  
Clinical Trial ◽  
Vitamin D ◽  
Bone Turnover ◽  
Bone Turnover Markers ◽  
Mineral Density ◽  
Double Blind ◽  
Treatment Of Osteoporosis ◽  
Dihydroxyvitamin D ◽  
Ovx Rats ◽  
Turnover Markers

Vitamin D supplementation is recommended whenever patients are given therapeutic drugs for osteoporosis, to make their calcium (Ca) balance positive. Vitamin D is converted to 25-hydroxyvitamin D in the liver, and then activated to become 1α,25-dihydroxyvitamin D in the kidneys. The active vitamin D acts in the intestine to stimulate Ca absorption and maintain the Ca balance. 2β-(3-Hydroxypropyloxy)-1α,25-dihydroxyvitamin D3 (eldecalcitol) and 2-methylene-19-nor-(20S)-1α,25-dihydroxyvitamin D3 (2MD) are newly developed vitamin D analogs, with a substitution at the 2 position of 1α,25-dihydroxyvitamin D3 (calcitriol). Eldecalcitol and 2MD share common structural and biological characteristics. Both compounds increase serum Ca levels more markedly than calcitriol, increase bone mineral density (BMD), and improve bone strength in ovariectomized (OVX) rats. In a randomized, placebo-controlled, double-blind, 1 year clinical trial, eldecalcitol dose-dependently increased lumbar and hip BMD and suppressed bone turnover markers in patients with osteoporosis. Whereas, 2MD markedly increased the bone turnover markers, but it did not change the BMD of postmenopausal women with osteopenia in a 1 year clinical trial. After a randomized, double-blind, 3 year fracture-prevention trial comparing it with alfacalcidol, eldecalcitol was approved for the treatment of osteoporosis in Japan. On the other hand, the manufacturer discontinued the clinical development of 2MD. In this review, we discuss the similarities and differences between these 2 compounds, and the reasons why different outcomes resulted from their clinical trials.

scholarly journals Association between Bone Mineral Density and Bone Turnover Markers in Breast Cancer Patients and Bone-Only Metastasis

Medicina ◽  
2021 ◽  
Vol 57 (9) ◽  
pp. 880
Author(s):  
Berrin Papila Kundaktepe ◽  
Volkan Sozer ◽  
Fatih Orkun Kundaktepe ◽  
Sinem Durmus ◽  
Cigdem Papila ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Mineral Density ◽  
Bone Turnover ◽  
Bone Metastases ◽  
Bone Turnover Markers ◽  
Biochemical Markers ◽  
Cross Linking ◽  
Mineral Density ◽  
Turnover Markers ◽  
Age Range

Background and Objectives: The aim of this study was to determine the influence of bone turnover markers, namely the N-terminal cross-linking telopeptide (NTx) and alpha C-terminal cross-linking telopeptide of type I collagen (α-CTx), in detecting bone metastasis (bone-only) in breast cancer (BC) patients, as well as to determine whether this effect is related to changes in bone mineral density (BMD). Materials and Methods: The participants in this study comprised 30 postmenopausal BC patients with bone metastases (age range: 59.56 ± 9.02), 20 postmenopausal BC patients without bone metastases (age range: 55.30 ± 11.55), and 20 healthy postmenopausal female controls (age range: 55.55 ± 5.85). Bone turnover markers (serum NTx and urine α-CTx) were measured using the ELISA method. A densitometer using dual-energy X-ray absorptiometry (DEXA) was used to analyze the BMD, and tumor markers were measured using the chemiluminescent immunometric assay. Results: The corresponding levels of serum NTx (p = 0.004), parathyroid hormone (PTH) (p = 0.001), and urine α-CTx (p < 0.001) of BC patients were found to be higher than the standard levels. After the BC patients were divided into subgroups on the basis of the presence of metastasis, the urine α-CTx levels (p = 0.001) were seen to be at critically high levels in those patients suffering from BC with metastasis. Though the BMD values in the lumbar spine (p < 0.001) and femoral neck (p = 0.001) were found to be significantly low in BC patients, no statistically substantial difference in the BMD levels of BC patients suffering from metastasis was observed. It was observed that urine α-CTx (specificity: 70%; sensitivity: 85%) values are critical factors that differentiate BC patients with metastasis from BC patients without metastasis. Conclusions: We found that alterations in bone turnover could be detected by using the values of urine α-CTx while differentiating BC patients with metastasis from BC patients without metastasis. Using the biochemical markers of bone turnover and BMD together would be pertinent for determining the level of metastasis present and examining the efficiency of bone density preservation therapy. Ideally, BMD measurement would be evaluated together with biochemical markers.

Bone mineral density and bone turnover markers in patients with thyroid cancer and L-T4 suppressive therapy after 25 years of follow-up

2014 ◽  
Author(s):  
Mingo Dominguez Maria Luisa de ◽  
Sonsoles Guadalix Iglesias ◽  
Maria Begona Lopez Alvarez ◽  
Guillermo Martinez Diaz-Guerra ◽  
Federico Hawkins Carranza
Keyword(s):  
Bone Mineral Density ◽  
Thyroid Cancer ◽  
Bone Turnover ◽  
Bone Mineral ◽  
Bone Turnover Markers ◽  
Suppressive Therapy ◽  
Mineral Density ◽  
Turnover Markers
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