leuprolide and Fractures--Bone

Treatment for cancer may cause gonadal dysfunction and bone loss (cancer treatment-induced bone loss ; CTIBL) . Especially, endocrine therapies for breast cancer or prostate cancer carry a significant risk of CTIBL. Therapy-induced premature menopause in premenopausal breast cancer patients, aromatase inhibitor in postmenopausal breast cancer patients, and LHRH agonist with or without anti-androgen in prostate cancer patients may cause bone loss of 5% or more. RANKL (receptor activator of nuclear factor-κB ligand) antibody (denosumab) is effective for prevention of CTIBL and it may prevent CTIBL-induced fracture. During cancer treatment with gonadal dysfunction, bone mineral density should be carefully followed to avoid QOL impairment due to osoteoporosis.

Topics: Androgen Antagonists; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Aromatase Inhibitors; Denosumab; Fractures, Bone; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Osteoporosis; RANK Ligand; Selective Estrogen Receptor Modulators

To investigate changes in bone mineral density (BMD) and fracture risk in men who received intermittent androgen deprivation (IAD) for nonmetastatic, hormone-sensitive prostate cancer.. Men with prostate cancer who lacked radiographically detectable metastases were treated in a prospective trial of IAD. After 9 months of treatment with leuprolide and flutamide, androgen deprivation therapy (ADT) was stopped until prostate-specific antigen reached a threshold (1 ng/mL for radical prostatectomy; 4 ng/mL for radiation or primary ADT) for a new cycle. Dual-energy x-ray absorptiometry (DXA) scans were performed before starting ADT and subsequently with each change in therapy. At least two consecutive DXA scans were required for this analysis. Computed tomography, bone scintigraphy, and lumbar spine x-rays were performed at the beginning and end of each treatment period.. Fifty-six of 100 patients met criteria for this analysis. The median age at study entry was 64.5 years (range, 49.8 to 80.9 years). The average percentage change in BMD during the first on-treatment period was -3.4% (P < .001) for the spine and -1.2% (P = .001) for the left hip. During the first off-treatment period (median, 37.4 weeks; range, 13.4 weeks to 8.7+ years), BMD recovery at the spine was significant, with an average percentage change of +1.4% (P = .002). Subsequent periods had heterogeneous changes of BMD without significant average changes. After a median of 5.5 years (range, 1.1 to 13.8+) years on trial, one patient (1.8%) had a compression fracture associated with trauma.. Patients experienced the greatest average change in BMD during early treatment periods of IAD with a smaller average change thereafter. Fractures were rare.

Topics: Absorptiometry, Photon; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Density; Bone Diseases, Metabolic; Drug Administration Schedule; Flutamide; Fractures, Bone; Humans; Leuprolide; Linear Models; Male; Middle Aged; Multivariate Analysis; Neoplasms, Hormone-Dependent; Osteoporosis; Prospective Studies; Prostatic Neoplasms; Risk Assessment; Risk Factors; Time Factors; Tomography, X-Ray Computed; Treatment Outcome

The objective of this study was to assess complex skeletal and metabolic changes in a single cohort of PCa patients taking long-term ADT.. Ninety-five patients with locally advanced PCa (mean age 73.3 ± 6.2 years) were treated with ADT for 24 months. Body mass index (BMI), waist-to-hip ratio (WHR), lipid profile, serum fasting glucose (SFG), and bone mineral density (BMD) of lumbar spine (L1-L4), femoral neck, and total hip BMD were examined at the baseline, and then every 12 months. These measurements were also made to the control group of 88 patients (mean age, 71.9 ± 6.7 years).. After 12 months of ADT, BMI, WHR, low-density lipoprotein, overall cholesterol, and SFG increased significantly; and total hip BMD and BMD L1-L4 decreased significantly in the study group. After 24 months of ADT, BMI, WHR, and SFG increased significantly. BMD was significantly lower in L1-L4, femoral neck, and total hip. Four patients (4.2%) were diagnosed with new onset diabetes. Overall, the incidence of fractures after 24 months of ADT was 7-fold higher in the study group.. ADT leads into unfavorable changes in body composition, unfavorable lipoprotein profile, increase in SFG level and decrease in BMD. The incidence of fractures was 7-fold higher in the study group.

Topics: Aged; Antineoplastic Agents, Hormonal; Blood Glucose; Body Mass Index; Bone Density; Case-Control Studies; Combined Modality Therapy; Femur Neck; Fractures, Bone; Hip; Humans; Leuprolide; Lipid Metabolism; Lipids; Male; Prostatic Neoplasms; Waist-Hip Ratio

Patients receiving androgen deprivation therapy undergo a rapid decline in bone mineral density during the first 6 to 12 months of initiating therapy. The World Health Organization has developed and implemented the Fracture Risk Assessment Tool (FRAX) to predict the ten year risk of a major fracture & hip fracture. Additionally, the National Comprehensive Cancer Network and the National Osteoporosis Foundation have developed osteoporosis guidelines. This study aims to characterize the fracture risk (based on the FRAX tool) and the current management of bone health based on national guidelines compliance.. A retrospective chart review of patients receiving a LHRH agonist at our institution was conducted. Data collection commenced upon Institutional Review Board approval and included demographics, past medical history, medication regimen, history of androgen deprivation therapy, bone health and its management. The ten year fracture risk calculated with the collected information using the FRAX tool.. A total of 174 subjects included with a mean age of 65.5 years, 71.8% had stage II prostate cancer, 97.7% received the LHRH agonist leuprolide for a mean of 13.8 ± 18.1 months. In addition to ADT, 57% of patients had ≥ 2 risk factors for developing osteoporosis. The risk of sustaining a major fracture increased from 4% to 5.6% after the initiation of ADT (P = <0.001). The risk for sustaining a hip fracture rose from 1.3% to 2.2% (P = <0.001). National guideline compliance was found to be 9%, 5% and 3% respectively for obtaining Dual Energy X-ray Absorptiometry (DEXA) scans, calcium supplementation, and vitamin D supplementation.. In addition to predisposing risk factors for osteoporosis, ADT significantly increases the fracture risk in the prostate cancer population. There is room for improvement in the management of bone health as some intervention could have been made in over 90% of patients evaluated.

Topics: Absorptiometry, Photon; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Bone Density; Calcium; Fractures, Bone; Gonadotropin-Releasing Hormone; Guideline Adherence; Humans; Leuprolide; Male; Middle Aged; Osteoporosis; Practice Guidelines as Topic; Prostatic Neoplasms; Retrospective Studies; Risk Factors; Vitamin D

Permanent androgen ablation has been the mainstay of treatment for advanced prostate cancer. However, the favorable outcome seen in recent pilot studies of intermittent androgen ablation raises the possibility of overtreatment.. This study included 35 Japanese men with advanced prostate cancer. Initial androgen ablation continued for 2 months after PSA levels decreased to <4.0 ng/ml, then was withdrawn. Androgen ablation was reinstituted 2 months after PSA reached levels >10 ng/ml, when indicated clinically or on patient request. Cycling continued until androgen independence was reached.. Mean follow-up was 21.0 months, representing an average of 2.5 cycles. Nine patients developed androgen independence at an average of 16.0 months following androgen ablation; three of these have died. Six of the nine patients with early biochemical progression had elevated alkaline phosphatase levels at entry; five of these exhibited a flare in alkaline phosphatase activity after initiation of androgen ablation. Mean bone mineral density (BMD) in the lumbar spines of 17 patients was 81.5 mg/cm3 at 23 months following therapy. The BMD of 10 of these patients was normal for their age. Four patients suffered bone fractures, none pathological.. Intermittent androgen ablation may be an option for patients with advanced prostate cancer and may be especially beneficial for those with initially low BMD levels. Patients with elevated alkaline phosphatase levels at entry or a flare in its activity may not be ideal candidates. Whether prolonging time to androgen independence will provide benefit remains to be investigated in a randomized, prospective study.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Alkaline Phosphatase; Androgen Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Density; Disease Progression; Drug Administration Schedule; Flutamide; Follow-Up Studies; Fractures, Bone; Goserelin; Humans; Leuprolide; Lumbar Vertebrae; Male; Middle Aged; Pilot Projects; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Remission Induction; Survival Rate; Testosterone; Treatment Outcome

Luteinizing hormone-releasing hormone (LHRH) agonists are popularly used drugs in the treatment of prostatic cancer. However, it has been reported that continuation of a low testosterone level following a longterm administration of these drugs reduces the bone mineral density and makes for osteoporosis, which is accountable for fracture, we measured the bone mineral density and bone metabolic markers in the cases who suffered fracture receiving LHRH agonists for prostatic cancer.. Between 1994 and 1998, 196 patients (mean age 78.1 years) were treated with LHRH agonists for prostatic cancer. Of these patients, 13(7%) who had bone fracture during treated with LHRH agonists were divided into fracture group, and 70 patients who had not bone fracture divided into non-fracture group. Fracture by traffic accident was excluded. The bone density in the third lumbar vertebra was measured using quantitative computed tomography (QCT). Osteocalcin, 1, 25- (OH)2 vitamin D, urinary type 1 collagen cross-linked N-telopeptides (NTx), parathyroid hormone (PTH) and calcitonin were measured as bone metabolic markers.. The mean age of fractured cases was 78 years. The period from the start of treatment to fracture was 11 to 45 months (mean 27 months). No case of fracture at the site of metastasis of prostatic cancer was found. The bone density was significantly low in the fracture group compared with that of non-fracture group. Of the bone metabolic markers, NTx showed high values in the fracture group.. There is a need to measure bone mineral density and bone metabolic markers periodically and to evaluate secondary osteoporosis in the patients receiving LHRH agonists for prostatic cancer.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Bone Density; Fractures, Bone; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Osteoporosis; Prostatic Neoplasms; Spine