leuprolide and Bone-Diseases--Metabolic

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 aim of this study was to evaluate bone mass changes after 1 year of four different types of pharmacological intervention. Ninety-seven prostate cancer patients treated with androgen deprivation therapy, and severe osteopenia or osteoporosis were retrospectively studied. Patients were divided in four groups. Group 1: 28 patients treated with denosumab, Group 2: 24 patients treated with alendronate, Group 3: 24 patients with no antiresorptive treatment and Group 4: 21 patients previously treated with alendronate and switched to denosumab. Dual X-ray absorptiometry was performed at baseline and after 1 year. Bone mass changes at the L2-L4 lumbar spine, femoral neck and total hip were evaluated. No differences were found at baseline. After 1 year, men receiving denosumab or alendronate (Group 1 and 2) showed a significant bone mass increase at the lumbar spine (+2.4 and +5.0 %, respectively), while no significant changes were observed in Group 3 and 4. At the femoral neck, Group 1 and 2 patients showed a significant bone mass increase (+3.7 and +3.6 %, respectively), while no significant changes were observed in Group 3 and 4. At the total hip, we observed a significant bone mass increase in Group 1 (+2.9 %) and a significant bone mass loss in Group 3 patients (-1.9 %). No significant changes were observed in Group 2 and 4. Denosumab increased significantly bone mass in all three dual X-ray absorptiometry standard sites, while alendronate did not at total hip. No benefit was observed in men previously treated with alendronate who switched to denosumab treatment.

Topics: Aged; Aged, 80 and over; Alendronate; Androgen Antagonists; Anilides; Antibodies, Monoclonal, Humanized; Bone Density Conservation Agents; Bone Diseases, Metabolic; Denosumab; Femur Neck; Humans; Leuprolide; Lumbar Vertebrae; Male; Nitriles; Osteoporosis; Prostatic Neoplasms; Radiography; Tosyl Compounds

We characterize the consequences of androgen deprivation therapy on body composition in elderly men.. Using a dual energy x-ray absorptiometry instrument, we determined the changes in bone mineral density, bone mineral content, fat body mass and lean body mass in 35 patients with prostate cancer without bone metastases who received luteinizing hormone releasing hormone analogue for 12 months.. At baseline conditions 46% of cases were classified as osteopenic and 14% as osteoporotic at the lumbar spine and 40% were osteopenic and 4% osteoporotic at the hip. Androgen deprivation significantly decreased bone mineral density either at the lumbar spine (mean gm./cm.2 [SD] 1.00 [0.194], 0.986 [0.172] and 0.977 [0.182] at baseline, and 6 and 12 months, respectively, p <0.002) or the hip (0.929 [0.136], 0.926 [0.144] and 0.923 [0.138], p <0.03). A more than 2% decrease in bone mineral density was found at the lumbar spine in 19 men (54.3%) and at the hip in 15 (42.9%). Bone mineral content paralleled the bone mineral density pattern. Lean body mass decreased (mean gm. [SD] 50,287 [6,656], 49,296 [6,554] and 49,327 [6,345], p <0.003), whereas fat body mass consistently increased (18,115 [6,209], 20,724 [6,029] and 21,604 [5,923] p <0.001).. Serial bone densitometry evaluation during androgen deprivation therapy may allow the detection of patients with prostate cancer at risk for osteoporotic fractures, that is those with osteopenia or osteoporosis at baseline and fast bone loss. The change in body composition may predispose patients to accidental falls, thus increasing the risk of bone fracture.

Topics: Absorptiometry, Photon; Adipose Tissue; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Body Composition; Body Mass Index; Bone Density; Bone Diseases, Metabolic; Flutamide; Hip Joint; Humans; Leuprolide; Lumbar Vertebrae; Male; Middle Aged; Osteoporosis; Prostatic Neoplasms; Thinness

We investigated the effects of conjugated estrogens as an add-back replacement drug, incadronate sodium as a bisphosphonate, and alfacalcidol as a vitamin D(3) analog on femoral bone mineral density (BMD) and bone mineral content (BMC) in female rats chronically treated with the gonadotropin-releasing hormone (GnRH) agonist leuprorelin acetate. The chemical castration of the rats by the administration of GnRH agonist for 16 weeks reduced the BMD values to 92.3%, 91.3%, and 93.3% of those of the normal control animals in the whole femur, metaphysis, and diaphysis of the femur, respectively. The BMC value was decreased to 91.0% of that of the normal control animals by the chronic GnRH agonist treatment. However, a simultaneous 8-week administration of conjugated estrogens, bisphosphonate, and vitamin D(3) analog markedly augmented the BMC values to 110.3%, 110.1%, and 114.4%, respectively, of those in the rats treated with the GnRH agonist alone. These findings indicate that antiosteoporotic agents could be useful for preventing induced osteopenia under the careful monitoring of biochemical markers of osteoblastic activity or bone resorption and BMD or BMC in patients undergoing GnRH treatment.

Topics: Animals; Body Weight; Bone Density; Bone Diseases, Metabolic; Diphosphonates; Estradiol; Estrogens, Conjugated (USP); Female; Femur; Fertility Agents, Female; Follicle Stimulating Hormone; Hydroxycholecalciferols; Leuprolide; Luteinizing Hormone; Organ Size; Ovariectomy; Radiography; Rats; Rats, Sprague-Dawley

Pharmacological inhibition of ovarian function (PIOF) in young women is associated with hypoestrogenism and very low estrogen levels. These alterations can trigger osteopenia, either by delayed peak bone mass or by active bone destruction, and therefore, an increased risk of osteoporosis at later years. Twenty-one women (mean age: 32 years) with diagnosis of endometriosis, who were submitted to PIOF with leuprolide acetate, were prospectively studied. As a result of treatment for bone resorption with nasal spray salmon calcitonin, 200 UI/day, a decreased femoral and lumbar bone mass density was identified in these women through densitometry. Regarding bone remodelling biochemistry, changes were seen in urinary markers suggesting bone destruction inhibition, while bone formation markers showed stimulation. Biochemical markers of bone turnover and bone mass measurements are useful during follow-up of young women with osteopenia.

Topics: Administration, Intranasal; Adult; Analysis of Variance; Bone Density; Bone Diseases, Metabolic; Bone Remodeling; Calcitonin; Depression, Chemical; Endometriosis; Female; Humans; Leuprolide; Ovary; Prospective Studies