Bone Fractures In Men Research Articles

8377 Associations of Serum Testosterone and Sex Hormone-Binding Globulin with Incident Fractures in Middle-Aged to Older Men

Abstract Disclosure: L. Grahnemo: None. R.J. Marriott: None. K. Murray: None. L. Tyack: None. M. Nethander: None. A.M. Matsumoto: None. E.S. Orwoll: None. D. Vanderschueren: None. B.B. Yeap: None. C. Ohlsson: None. As men age, their circulating testosterone (T) decreases, circulating sex-hormone binding globulin (SHBG) increases, and risk of bone fracture increases. Unexpectedly, a recent large clinical trial reported that T treatment increased fracture risk in men. It is unclear if circulating T, independently of comorbidities, is associated with male fracture risk. We tested the hypothesis that serum T concentration is an independent risk predictor for incident bone fractures in men. We analyzed associations for T and SHBG with incident fractures in the large and well-characterized UK Biobank cohort (205,973 male participants median age 58 years, excluding men on androgen-related therapies). Baseline serum total T and SHBG were measured by immunoassay, and incident fractures documented over a median follow-up of 13.6 years (11,088 any fracture cases; 1,680 hip fracture cases; 1,366 forearm fracture cases). Associations of hormonal variables with fracture outcomes were modelled using Cox regression, adjusted for multiple comorbidities/covariates, with imputation for missing data, and non-linearity assessed using cubic splines. For total T, in multivariable models not including SHBG, there was a non-linear association with any fracture and hip fractures but not forearm fractures, with the lowest risk in the second quintile (Q2; hazard ratio (HR), 95% confidence intervals (CIs) Q2 vs Q5 any fracture 0.89, 0.84-0.94; hip fracture 0.76, 0.66-0.87; forearm fracture 0.97, 0.83-1.13). However, in multivariable models analyzing total T which were adjusted for SHBG, lower total T was associated with higher risk for fractures at all evaluated bone sites (HR, 95% CIs Q1 vs Q5 any fracture 1.24, 1.16-1.33; hip fracture 1.28, 1.08-1.51; forearm fracture 1.51, 1.25-1.82). Similar results were seen in multivariable models using calculated free T values. Lower SHBG concentration was associated with lower risk of any fracture, hip fractures, and forearm fractures, in multivariable models not including total T (HR, 95% CIs Q1 vs Q5, any fracture 0.71, 0.67-0.75; hip fracture 0.55, 0.47-0.65; forearm fracture 0.62, 0.52-0.74), with similar results following additional adjustment for total T. In conclusion, associations of total T concentrations with fracture risk without adjustment for SHBG are non-linear and inconsistent, whereas lower total T concentration, adjusted for SHBG, was independently associated with higher risks of any fracture, hip fractures, and forearm fractures. Lower circulating SHBG, without or with adjustment for total T, was strongly associated with lower risk of fractures at all three sites, consistent with SHBG being a major independent biomarker of fracture risk in men. When examining the relationship of endogenous T concentrations with health outcomes influenced by androgen-sensitive tissues in middle-aged to older men, both total T and SHBG concentrations should be assessed. Presentation: 6/2/2024

Proton pump inhibitors increase risk of bone fractures in men with cirrhosis: a population-based study.

Bone fractures are a frequent complication in patients with cirrhosis. Proton pump inhibitors (PPIs) are among the most frequently prescribed medications and may impair bone quality and quantity. To investigate whether PPI use predisposes patients with cirrhosis to bone fractures. We performed a population-based case-control study exploring a sample of patients with cirrhosis derived from the Disease Analyzer database. In total, 1795 cirrhotic patients with fractures were compared to 10235 cirrhotic patients without fractures. PPI use overall and the cumulative PPI dose 5years prior to the index date were analysed. To estimate the association between PPI use and fractures, logistic regression analyses were performed taking cofounding factors into consideration. PPI use was more frequently seen in cirrhotic patients with fractures compared to controls (67.0% vs 53.4%, P<0.001). In regression analyses, PPI use was associated with bone fractures after adjusting for important confounders (OR 1.34, 95% CI 1.20-1.51, P<0.001). Importantly, the strongest effect of PPIs on bone fractures was seen in men and patients below 70years of age. On further sensitivity analyses, we observed a dose-dependent effect for all PPIs with the strongest effect in cirrhotic patients receiving a dose of >50000mg during the 5years prior to index date (OR 1.63, 95% CI 1.32-2.03). PPI use was associated with bone fractures in a dose-dependent fashion in patients with cirrhosis. PPI use in these patients should be based on a careful risk-benefit assessment.

Androgen Deprivation Therapy Induces Vitamin K Loss in Men with Prostate Cancer

Bone strength is determined by bone mineral density (BMD) and bone quality. Bone fractures are serious adverse events in men receiving androgen deprivation therapy (ADT) for prostate cancer. Although it is established that ADT reduces BMD, it is unclear how ADT alters bone quality. Vitamin K is a bone quality marker which aids to carboxylates osteocalcin to form bone matrix. Serum undercarboxylated osteocalcin (ucOC) is accumulated in vitamin K deficiency, which is used as a surrogate for vitamin K status. As little is known as to the impact of ADT on serum ucOC, we investigated the changes of serum ucOC in PC patients during ADT. Fifty consecutive hormone naive PC patients were enrolled. Serum ucOC, serum osteocalcin (OC), serum Nteloptide of type 1 collagen (NTx) and hip bone mineral density (BMD) were measured at baseline, 6 month and 12 months since the start of ADT. Serum ucOC levels at 6 and 12 months (3.86 ± 2.28 and 4.32 ± 1.76 ng/ml) were significantly higher than those at baseline (2.46 ± 1.46 ng/ml). Serum OC levels at 12 months (7.82 ± 2.65 ng/ml) were significantly higher than those at baseline (5.26 ± 1.86 ng/ml). Furthermore, the ratio of ucOC/OC at 1 year (0.54 ± 0.15) were significantly higher than at baseline (0.42 ± 0.18). Both serum NTx levels and hip BMDs at 6 and 12 months were also significantly higher than those at baseline. Our results first demonstrated that ADT induced vitamin K loss in men with prostate cancer. Further investigations are required to determine whether vitamin K supplement is useful to prevent bone fractures in men on ADT.

Serum leptin, bone mineral density and the healing of long bone fractures in men with spinal cord injury

Previously reported fracture rates in patients with spinal cord injury range from 1% to 20%. However, the exact role of spinal cord injury in bone metabolism has not yet been clarified. In order to investigate the effects of serum leptin and bone mineral density on the healing of long bone fractures in men with spinal cord injury, 15 male SCI patients and 15 matched controls were involved in our study. The outcome indicated that at 4 and 8 weeks after bone fracture, callus production in patients with spinal cord injury was lower than that in controls. Besides, bone mineral density was significantly reduced at 2, 4 and 8 weeks. In addition, it was found that at each time point, patients with spinal cord injury had significantly higher serum leptin levels than controls and no association was found between serum leptin level and bone mineral density of lumbar vertebrae. Moreover, bone mineral density was positively correlated with bone formation in both of the groups. These findings suggest that in early phases i.e. week 4 and 8, fracture healing was impaired in patients with spinal cord injury and that various factors participated in the complicated healing process, such as hormonal and mechanical factors.

MP70-17 OPTIMAL TESTOSTERONE SUPPRESSION ON MEDICAL ANDROGEN DEPRIVATION THERAPY SHOULD STRIVE TO SUPPRESS FREE TESTOSTERONE LEVELS, TO LEVELS SIMILAR TO ORCHIECTOMY--WHAT IS THAT VALUE?

You have accessJournal of UrologyProstate Cancer: Advanced II1 Apr 2014MP70-17 OPTIMAL TESTOSTERONE SUPPRESSION ON MEDICAL ANDROGEN DEPRIVATION THERAPY SHOULD STRIVE TO SUPPRESS FREE TESTOSTERONE LEVELS, TO LEVELS SIMILAR TO ORCHIECTOMY--WHAT IS THAT VALUE? Evan Yu, Robert Getzenberg, Jordan Smith, Michael Hancock, Matthew Smith, S Bruce Malkowixz, Paul Sieber, James Dalton, and Mitchell Steiner Evan YuEvan Yu More articles by this author , Robert GetzenbergRobert Getzenberg More articles by this author , Jordan SmithJordan Smith More articles by this author , Michael HancockMichael Hancock More articles by this author , Matthew SmithMatthew Smith More articles by this author , S Bruce MalkowixzS Bruce Malkowixz More articles by this author , Paul SieberPaul Sieber More articles by this author , James DaltonJames Dalton More articles by this author , and Mitchell SteinerMitchell Steiner More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.2215AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The goal of medical androgen deprivation therapy (ADT) for advanced prostate cancer is to provide an equivalency to orchiectomy based upon older assays for serum testosterone. Literature shows that based on more modern assays, medical ADT does not always provide optimal testosterone suppression equivalent to orchiectomy. With the understanding that free, or unbound, testosterone is the biologically and clinically relevant component, the therapeutic goal of ADT should be to decrease free testosterone to levels similar to orchiectomy. Free testosterone has not been well studied in a substantial number of orchiectomized men. The purpose of this study was to examine a subpopulation of orchiectomized men in a clinical trial to determine the level of serum free testosterone in advanced prostate cancer. METHODS Baseline data was utilized from a double blind, randomized, placebo controlled trial (G300203) to determine the capacity of toremifene 80 mg to prevent bone fractures in men on ADT. This study included 1,389 men from 150 sites in the US and Mexico. Baseline characteristics, including whether men were on medical ADT or status post orchiectomy, were available. Serum free testosterone levels were assayed at baseline by radioimmunoassay (RIA) (Diagnostic Products Corporation) and are reported for men who underwent orchiectomy. RESULTS A subpopulation of 114 men underwent orchiectomy. Median age was 76 years (range 51-90). Median serum free testosterone level was 0.92 pg/ml (min. 0.35 pg/ml and max. 33.95 pg/ml) with a mean level of 1.71 pg/ml ± 2.77. CONCLUSIONS This study is believed to be the largest cohort in which serum free testosterone levels have been reported in men who underwent orchiectomy. In this cohort, median serum free testosterone is approximately 0.9 pg/ml. This value could be considered to be the optimal testosterone suppression of free testosterone with orchiectomy and represents the goal of medical ADT. At the time this study was performed, RIA was considered to be the standard but has since been shown to underestimate serum free testosterone levels by 20-60%. Currently, equilibrium dialysis coupled with LC-MS/MS is the gold standard, but the results from this analysis provide us with increased understanding of the optimal level of free testosterone in treating advanced prostate cancer. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e812 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Evan Yu More articles by this author Robert Getzenberg More articles by this author Jordan Smith More articles by this author Michael Hancock More articles by this author Matthew Smith More articles by this author S Bruce Malkowixz More articles by this author Paul Sieber More articles by this author James Dalton More articles by this author Mitchell Steiner More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP70-18 MORTALITY IN MEN WITH ADVANCED PROSTATE CANCER MAY BE REDUCED WITH RADICAL TREATMENT COMPARED TO ANDROGEN DEPRIVATION ALONE

You have accessJournal of UrologyProstate Cancer: Advanced II1 Apr 2014MP70-18 MORTALITY IN MEN WITH ADVANCED PROSTATE CANCER MAY BE REDUCED WITH RADICAL TREATMENT COMPARED TO ANDROGEN DEPRIVATION ALONE Prasanna Sooriakumaran, Tommy Nyberg, Olof Akre, Stefan Carlsson, Leif Haendler, Gunnar Steineck, and Peter Wiklund Prasanna SooriakumaranPrasanna Sooriakumaran More articles by this author , Tommy NybergTommy Nyberg More articles by this author , Olof AkreOlof Akre More articles by this author , Stefan CarlssonStefan Carlsson More articles by this author , Leif HaendlerLeif Haendler More articles by this author , Gunnar SteineckGunnar Steineck More articles by this author , and Peter WiklundPeter Wiklund More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.2216AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Standard management for men with advanced prostate cancer is androgen deprivation therapy (ADT) alone. Our objective was to evaluate whether radical treatment of the primary tumor in men with advanced prostate cancer improved survival over those managed with ADT alone. METHODS The National Prostate Cancer Registry of Sweden is linked to eight national datasets to form PCBaSe and provides >98% complete information on virtually all patient and tumor covariates of all prostate cancer cases in Sweden diagnosed from 1996. We abstracted data from PCBaSe on men with PSA>50 or M+ or T4 disease, and matched them exactly for grade, T-stage, M-stage, and Charlson comorbidity index (CCI). We produced cumulative incidence curves (CICs) as well as performed statistical adjustments via classical regression techniques and propensity scoring, to compare prostate cancer mortality (PCM) and other cause mortality (OCM) in those men treated with ADT as primary therapy versus those treated initially with radical therapy (surgery or radiotherapy). RESULTS The matched sample was 699 cases per group. CICs demonstrated lower PCM (dark blue/orange) and OCM (light blue/orange) in the radical treatment group compared to the ADT group up to 14 years follow-up (Figure). Propensity score-adjusted subdistribution hazard ratios (sHR) for ADT versus radical treatment were 2.89 (95% CI, 2.25-3.71) for PCM and 1.41 (95% CI, 1.01-1.98) for OCM. A post-hoc sensitivity analysis found that a residual confounder differentially prevalent in 90% versus 10% in the ADT and radical treatment groups respectively would need a sHR of 4.09 to account for the above PCM point estimate, with still higher confounder sHR for less skewed confounder prevalences. CONCLUSIONS This large, observational study from a comprehensive dataset suggests that men with advanced prostate cancer might benefit in survival terms from being managed with radical therapy as their primary treatment rather than ADT alone. Confounding is highly unlikely to account for these results, and this study provides an epidemiologic rationale to consider a future RCT in this setting. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e812-e813 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Prasanna Sooriakumaran More articles by this author Tommy Nyberg More articles by this author Olof Akre More articles by this author Stefan Carlsson More articles by this author Leif Haendler More articles by this author Gunnar Steineck More articles by this author Peter Wiklund More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Optimal testosterone suppression on medical ADT should strive to suppress free testosterone levels to levels similar to orchiectomy: What is that value?

144 Background: The goal of medical androgen deprivation therapy (ADT) for advanced prostate cancer is to provide an equivalency to orchiectomy based upon older assays for serum testosterone (T). Literature shows that based on more modern assays, medical ADT does not always provide optimal total T suppression equivalent to orchiectomy. With the understanding that free, or unbound, T is the biologically and clinically relevant component, the therapeutic goal of ADT should be to decrease free T to levels similar to orchiectomy. Free T has not been well studied in a substantial number of orchiectomized men. The purpose of this study was to examine a subpopulation of orchiectomized men in a clinical trial to determine the level of serum-free T in advanced prostate cancer. Methods: Baseline data was utilized from a double blind, randomized, placebo controlled trial (G300203) to determine the capacity of toremifene 80 mg to prevent bone fractures in men on ADT. This study included 1,389 men from 150 sites in the U.S. and Mexico. Baseline characteristics, including whether men were on medical ADT or status post orchiectomy, were available. Free T levels were assayed at baseline by radioimmunoassay (RIA) (Diagnostic Products Corporation) and are reported for men who underwent orchiectomy. Results: A subpopulation of 114 men underwent orchiectomy. Median age was 76 (range 51 to 90). Median serum free T level was 0.92 pg/ml (min. 0.35 pg/ml and max. 33.95 pg/ml) with a mean level of 1.71 pg/ml ± 2.77. Conclusions: This study is believed to be the largest cohort in which free T levels have been reported in men who underwent orchiectomy. In this cohort, median serum free T is approximately 0.9 pg/ml. This value could be considered to be the optimal testosterone suppression of free T with orchiectomy and represents the goal of medical ADT. At the time this study was performed, RIA was considered to be the standard but has since been shown to underestimate free T levels by 20 to 60%. Currently, equilibrium dialysis coupled with LC-MS/MS is the gold standard, but the results from this analysis provide us with increased understanding of the optimal level of free T in treating advanced prostate cancer. Clinical trial information: NCT00129142.

Drug interaction potential of toremifene and N-desmethyltoremifene with multiple cytochrome P450 isoforms

Toremifene is an effective agent for the treatment of breast cancer in postmenopausal women and is being evaluated for its ability to prevent bone fractures in men with prostate cancer taking androgen deprivation therapy.Due to the potential for drug–drug interactions, the ability of toremifene and its primary circulating metabolite N-desmethyltoremifene (NDMT) to inhibit nine human cytochrome P450 (CYP) enzymes was determined using human liver microsomes. Induction of CYP1A2 and 3A4 by toremifene was also investigated in human hepatocytes.Toremifene did not significantly inhibit CYP1A2 or 2D6. However, toremifene is a competitive inhibitor of CYP3A4, non-competitive inhibitor of CYP2A6, 2C8, 2C9, 2C19 and 2E1 and mixed-type inhibitor of CYP2B6. CYP inhibition by NDMT was similar in magnitude to toremifene. Toremifene did not induce CYP1A2 but increased CYP3A4 monooxygenase activity and gene expression in drug-exposed human primary hepatocytes.Although clinical doses of toremifene produce steady state exposures to toremifene and NDMT that may be sufficient to cause pharmacokinetic drug–drug interactions with other drugs metabolised by CYP2B6, CYP2C8, CYP3A4, CYP2C9 and CYP2C19, these data indicate that toremifene is unlikely to play a role in clinical drug–drug interactions with substrate drugs of CYP1A2 and CYP2D6.

Bone mineral density and bone fracture in male patients receiving long-term suppressive levothyroxine treatment for differentiated thyroid carcinoma

Studies on the effect of exogenous subclinical thyrotoxicosis on bone mineral density (BMD) in male patients treated with suppressive doses of levothyroxine for differentiated thyroid carcinoma (DTC) are not conclusive. In order to evaluate BMD (in femoral neck, lumbar spine, and distal radius) and bone fractures in men under long-term suppressive treatment with levothyroxine for DTC, we conducted a cross-sectional, retrospective study in 33 Caucasian men (mean±SD age: 56±14years) under treatment for DTC. The control group comprised 33 healthy age- and body mass index-matched male volunteers. BMD was assessed by dual-energy X-ray absorptiometry (DXA). Bone turnover biomarkers (calcium, phosphate, alkaline phosphatase, PTH, vitamin D, urinary calcium, and N-Telopeptide/creatinine index) and testosterone were determined. Previous bone fractures were evaluated with a questionnaire and X-ray images of thoracic and lumbar vertebrae. Patients were treated for a mean duration of 15±5years. No differences were found between patients and controls in bone turnover biomarkers or areal BMD, T-scores or Z-scores in all sites evaluated. No earlier fractures or pain episodes were registered in either group and the incidence of asymptomatic vertebral fractures did not differ significantly between patient (18.8%) and control groups (16.7%), (P=0.9). In conclusion, long-term suppressive treatment with levothyroxine in men with DTC does not appear to exert deleterious effects on bone mineral density or increase the prevalence of fracture.

Bone Fractures and Hypoglycemic Treatment in Type 2 Diabetic Patients

OBJECTIVE—Hypoglycemic treatments could modulate the risk for fractures in many ways. Most studies have not explored the effect on the incidence of bone fractures of individual oral hypoglycemic agents, rather all oral treatments as a whole. The aim of this case-control study, nested within a retrospective cohort, is the assessment of the risk for bone fractures associated with exposure to insulin or different oral hypoglycemic agents. RESEARCH DESIGN AND METHODS—A case-control study nested within a cohort of 1,945 diabetic outpatients with a follow-up of 4.1 ± 2.3 years was performed, comparing 83 case subjects of bone fractures and 249 control subjects matched for age, sex, duration of diabetes, BMI, A1C, comorbidity, smoking, and alcohol abuse. Exposure to hypoglycemic drugs during the 10 years preceding the event (or matching index date) was assessed. RESULTS—In a model including treatment with insulin secretagogues metformin and insulin for at least 36 months during the previous 10 years, no significant association was observed between bone fractures and medications. In an alternative model considering treatments at the time of fracture, insulin treatment was significantly associated with bone fractures in men (OR 3.20 [95% CI 1.32–7.74]) but not in women (1.41 [0.73–2.73]). CONCLUSIONS—Insulin-sensitizing treatment with metformin is not associated with a higher incidence of bone fractures, suggesting that the negative effect of thiazolidinediones is due to a specific action on bone metabolism rather a reduction of insulinemia. Conversely, current treatment with insulin increases the risk of fractures; at the same time, exposure to this agent in the longer term does not appear to affect bone frailty.

Can toremifene prevent bone loss in the orchiectomized rat?

8108 Background: Androgen-deprivation therapy leads to osteoporosis and bone fractures in men with prostate cancer. Selective estrogen receptor modulators (SERMs) which reduce bone resorption in females may also prevent osteoporosis and fractures in males. We tested the efficacy of toremifene (Tor), a SERM, to prevent bone loss in the castrated male rat. Methods: In a 6-wk study, fifty 8 mo-old male rats were divided into 5 groups (n=10): Sham, Orchiectomy (Orx), Orx+Tor (5mg/kg/d), Orx+Tor (10 mg/kg/d) and Orx+Estradiol (E, 0.2mg/kg/ml control). Treatment was initiated at castration via s.c. pump. Serum bone biomarkers osteocalcin (OC) and C-terminal telopeptides (CTX) were measured at 0, 1.5, 4 and 6 wks by ELISA. Prostate was weighed at necropsy. Tibia was analyzed by histomorphometry. Femur bone mineral density (BMD) and mechanical strength were measured by DEXA and Compression test, respectively. Results: Orx decreased prostate weight by 77%, significantly increased OC and CTX levels, decreased trabecular bone volume, and increased bone turnover significantly (p<0.05, orx vs. sham and treated groups). Orx increased osteoclast number, mineralization surface and bone formation rate (BFR/BS, BFR/BV, BFR/TV). E, 5 mg-Tor and 10 mg-Tor significantly reversed the Orx-related increase in OC and CTX levels, the effect of Tor being dose- and time-dependent. The Orx-induced increase in bone turnover parameters was also reversed by both E and Tor although the change was statistically nonsignificant. Orx resulted in loss of BMD in proximal- and distal-femur and while 5 mg-Tor was ineffective 10 mg-Tor and E prevented this loss. Both E and 10 mg-Tor had equal effect on the proximal-femur BMD and the effect of E on distal-femur was significant (p ≤ 0.01, E vs. Orx group). No statistically significant difference was observed in femur strength between Tor or E versus the Orx group. E or Tor had no effect on prostate weight in the Orx rat. Conclusions: Toremifene reduced bone turnover, prevented bone density loss and protected bone microarchitecture in the Orx rat. These studies suggest that toremifene may prevent bone loss and protect bone quality in prostate cancer patients treated by androgen-deprivation therapy. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GTx, Inc. GTx, Inc.

Can toremifene prevent bone loss in the orchiectomized rat?

8108 Background: Androgen-deprivation therapy leads to osteoporosis and bone fractures in men with prostate cancer. Selective estrogen receptor modulators (SERMs) which reduce bone resorption in females may also prevent osteoporosis and fractures in males. We tested the efficacy of toremifene (Tor), a SERM, to prevent bone loss in the castrated male rat. Methods: In a 6-wk study, fifty 8 mo-old male rats were divided into 5 groups (n=10): Sham, Orchiectomy (Orx), Orx+Tor (5mg/kg/d), Orx+Tor (10 mg/kg/d) and Orx+Estradiol (E, 0.2mg/kg/ml control). Treatment was initiated at castration via s.c. pump. Serum bone biomarkers osteocalcin (OC) and C-terminal telopeptides (CTX) were measured at 0, 1.5, 4 and 6 wks by ELISA. Prostate was weighed at necropsy. Tibia was analyzed by histomorphometry. Femur bone mineral density (BMD) and mechanical strength were measured by DEXA and Compression test, respectively. Results: Orx decreased prostate weight by 77%, significantly increased OC and CTX levels, decreased trabecular bone volume, and increased bone turnover significantly (p<0.05, orx vs. sham and treated groups). Orx increased osteoclast number, mineralization surface and bone formation rate (BFR/BS, BFR/BV, BFR/TV). E, 5 mg-Tor and 10 mg-Tor significantly reversed the Orx-related increase in OC and CTX levels, the effect of Tor being dose- and time-dependent. The Orx-induced increase in bone turnover parameters was also reversed by both E and Tor although the change was statistically nonsignificant. Orx resulted in loss of BMD in proximal- and distal-femur and while 5 mg-Tor was ineffective 10 mg-Tor and E prevented this loss. Both E and 10 mg-Tor had equal effect on the proximal-femur BMD and the effect of E on distal-femur was significant (p ≤ 0.01, E vs. Orx group). No statistically significant difference was observed in femur strength between Tor or E versus the Orx group. E or Tor had no effect on prostate weight in the Orx rat. Conclusions: Toremifene reduced bone turnover, prevented bone density loss and protected bone microarchitecture in the Orx rat. These studies suggest that toremifene may prevent bone loss and protect bone quality in prostate cancer patients treated by androgen-deprivation therapy. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GTx, Inc. GTx, Inc.

Risk factors for male osteoporosis

Hypogonadism from long-term androgen deprivation therapy (ADT), either by bilateral orchiectomy or administration of gonadotropin-releasing hormone (GnRH) agonists, causes significant and accelerated bone loss that may increase the risk of bone fractures in men with prostate cancer. Recent reports, as well as new data from our institution, have shown a high prevalence of pre-existing osteopenia and osteoporosis in men with prostate cancer before receiving ADT, and this is of great concern because of the risk of further bone loss during ADT. Data from these studies suggest the urgent need for clinical guidelines for screening, prevention, and treatment of these cases. This article reviews the prevalence and risk factors associated with osteoporosis in men and addresses risk factors in men with prostate cancer not receiving ADT. Considerations for the patient selection and timing of bone densitometry will also be discussed.

Bone fractures associated with luteinizing hormone-releasing hormone agonists used in the treatment of prostate carcinoma.

Luteinizing hormone-releasing hormone agonists (LHRH-a) have become an established treatment for certain patients with prostate carcinoma. LHRH-a are known to decrease bone mineral density. The purpose of this study was to determine the risk of bone fracture in men receiving LHRH-a for prostate carcinoma. A retrospective chart review and phone interviews were conducted to determine the incidence of bone fractures occurring in patients receiving LHRH-a for the treatment of prostate carcinoma. Abstracted data included the number of monthly LHRH-a injections, age, clinical stage of disease, sites of metastases, and bone fracture history. Twenty of the 224 patients (9%) treated with LHRH-a for prostate carcinoma between 1988 and 1995 at 3 teaching hospitals had at least 1 bone fracture during treatment with LHRH-a. The duration of treatment to the time of fracture ranged from 1 to 96 months (mean, 22.2 months). Seven fractures (32%) were osteoporotic in nature (i.e., vertebral compression fractures or hip fractures after a fall from standing), whereas 8 fractures (36%) were associated with a significant traumatic event (i.e., a motor vehicle accident, boxing, etc.) and 5 were of mixed etiology. Two of 22 fractures (9%) were pathologic. This study demonstrated a 9% fracture incidence in a cohort of patients receiving LHRH-a for prostate carcinoma for up to 96 months. The incidence of osteoporotic fractures was 5%.