Androgen deprivation therapy for prostate cancer results in significant loss of bone density

doi:10.1016/S0090-4295(99)00301-5

Urology

Volume 54, Issue 4, October 1999, Pages 607-611

https://doi.org/10.1016/S0090-4295(99)00301-5 Get rights and content

Abstract

Objectives. Advanced prostate cancer is a frequently diagnosed condition in the aging male population, and many men will ultimately be treated with androgen deprivation therapy (ADT). Long-term consequences of ADT on bone mineral density (BMD) have not been systematically studied. We performed a pilot study to test the hypothesis that ADT in patients with prostate cancer results in the measurable loss of BMD.

Methods. A cross-sectional study of 32 men with prostate cancer who were about to begin ADT or who had been receiving ADT for more than 1 year was conducted. BMD was measured by single and dual energy x-ray absorptiometry in the lumbar spine, hip, and forearm. Linear regression analysis was used to estimate the time necessary to develop significant BMD loss in the spine, hip, and forearm regions.

Results. Five (63%) of 8 men who had not received ADT and 21 (88%) of 24 men who had received ADT for more than 1 year fulfilled the BMD criteria for osteopenia or osteoporosis at one or more sites. When BMD was compared at each site, men who received ADT for more than 1 year had significantly lower BMD in the lumbar spine than men who had not started treatment (P <0.05). On the basis of regression analysis, an estimated 48 months of ADT would be necessary to develop BMD criteria for osteopenia in the lumbar spine for a man with average BMD at the initiation of therapy.

Conclusions. Pre-existing osteopenia and osteoporosis were common in men with prostate cancer before initiating ADT. Both ADT and the duration of ADT were significantly associated with the loss of BMD in men with prostate cancer.

Section snippets

Subjects

This study was approved by the Human Subjects, Radiation Safety, and Research and Development Committees at the Veterans Affairs Medical Center, Ann Arbor, Michigan, and written informed consent was obtained from all patients. Patients with prostate cancer from the Urology and Medical Oncology clinics who were about to begin ADT or who had been receiving ADT for more than 1 year were asked to participate in this study. In all patients, the indications for ADT were either metastatic disease or

Clinical and demographic characteristics

A total of 32 patients completed the study protocol (Table I). All patients were treated with a luteinizing hormone-releasing hormone agonist; 1 subject subsequently underwent an orchiectomy because of his intolerance of the monthly subcutaneous injections. None of the patients in this study received long-term treatment with an oral nonsteroidal antiandrogen agent (eg, flutamide or bicalutamide). Seven of 32 subjects had bone metastases confirmed on bone scan, and 1 patient with widely

Comment

The use of ADT for advanced prostate cancer is a time-honored practice. However, ADT has been increasingly offered to patients who have a PSA or biochemical recurrence after primary therapy.6, 7 Given that many patients with prostate cancer are ultimately found to have recurrent disease after definitive therapy for localized disease,8, 9 this practice will result in large numbers of men being exposed to the effects of long-term systemic androgen depletion. To date, these consequences of ADT,

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Bone mineral density, structure, distribution and strength in men with prostate cancer treated with androgen deprivation therapy
2019, Bone
Citation Excerpt :
However, further studies using more advanced high resolution imaging techniques such as HR-pQCT are needed to address this question. Although previous cross-sectional studies investigating DXA aBMD in ADT-treated men compared to control groups have reported mixed results [9–14], we found that lumbar aBMD was ~7–8% lower in the ADT-treated men compared to PCa and healthy controls. This is consistent with the findings from several studies which also observed that lumbar spine aBMD in ADT-treated men was 8% to 23% lower compared to PCa controls [9,11,12] or healthy controls [9].
Androgen deprivation therapy (ADT) improves survival in men with advanced prostate cancer (PCa), but has been associated with compromised skeletal health and increased fracture risk. However, limited previous research has investigated determinants of bone strength beyond DXA-derived areal bone mineral density (aBMD) in this population group. The aim of this cross-sectional study was to investigate the effects of ADT in men with PCa on BMD, bone structure, estimates of whole bone strength and cortical bone distribution. A total of 70 ADT-treated men, 52 PCa controls and 70 healthy controls had DXA lumbar spine and proximal femur aBMD and pQCT distal (4%) and proximal (66%) tibia and radius cortical and trabecular volumetric BMD (vBMD), bone structure, strength and cortical bone distribution assessed. Analyses included BMI and/or tibia/radius length as covariates. On average, ADT-treated men had a higher BMI than PCa (P < 0.05) but not healthy controls. ADT-treated men had 7.2–7.8% lower lumbar spine aBMD than PCa (P = 0.037) and healthy controls (P = 0.010), with a trend for a lower total hip aBMD in the ADT-treated men (P = 0.07). At the distal tibia, total bone area was 6.2–7.3% greater in ADT-treated men than both controls (P < 0.01), but total vBMD was 8.4–8.7% lower in ADT-treated men than both controls (P < 0.01). Moreover, bone strength index (BSI) was 10.8% lower relative to healthy controls only (P < 0.05). At the distal radius, ADT-treated men had lower total and trabecular vBMD (10.7–14.8%, P < 0.05) and BSI (23.6–27.5%, P < 0.001) compared to both controls. There were no other differences in bone outcomes at the proximal tibia or radius. In conclusion, ADT treatment for PCa was associated with lower BMD and estimated compressive bone strength, particularly at trabecular skeletal sites (lumbar spine, and distal tibia and radius), compared to controls, but there were no consistent differences in cortical bone structure, distribution or bending strength.
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To explore how follicle-stimulating hormone (FSH) may contribute to cardiovascular, metabolic, skeletal, and cognitive events in men treated for prostate cancer, with various forms of androgen deprivation therapy (ADT).
A colloquium of prostate cancer experts was convened in May 2015, to discuss the role of FSH in the development of unwanted effects associated with ADT. Subsequently, a literature review (Medline, PubMed, and relevant congress abstract databases) was performed to further explore and evaluate the collected evidence.
It has become evident that, in the setting of ADT, FSH can promote the development of atherosclerotic plaque formation, metabolic syndrome, and insulin resistance. Data also suggest that FSH is an important mediator of bone remodeling, particularly bone resorption, and thereby increases the risk for bone fracture. Additional evidence implicates a role for FSH in bone metastasis as well. The influence of FSH on ADT-induced cognitive deficits awaits further elucidation; however, the possibility that FSH may be involved therein cannot be ruled out.
The widespread molecular and physiological consequences of FSH system activation in normal and pathological conditions are becoming better understood. Progress in this area has been achieved by the development of additional investigative and clinical measures to better evaluate specific adverse effects. More research is needed on FSH function in the development of cancer as well as its association with cardiovascular, metabolic, musculoskeletal, and cognitive effects in ADT.
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Osteoporose, uma doença metabólica caracterizada por baixa massa óssea, deterioração da microarquitetura do tecido ósseo e aumento da suscetibilidade a fraturas, é comumente vista como um problema de saúde feminino. Essa visão tem fundamentos: em comparação com os homens as mulheres têm densidade mineral óssea menor, têm vida mais longa e perdem massa óssea mais rapidamente, principalmente após a menopausa, devido à diminuição acentuada dos níveis séricos de estrógeno. Entretanto, nos últimos 20 anos a osteoporose no homem tem sido reconhecida como um problema de saúde pública devido à ocorrência cada vez maior de fraturas por fragilidade. Cerca de 30% de todas as fraturas de quadril ocorrem em homens. Estudos recentes mostram que a probabilidade de fratura por fragilidade do quadril, vértebra ou punho em homens brancos após os 50 anos, pelo resto de suas vidas, situa‐se em torno de 13%, 40% nas mulheres. Os homens apresentam perda de massa óssea e fraturas mais tardiamente do que as mulheres. Embora os homens mais idosos tenham maior risco de fratura, cerca de metade das fraturas de quadril ocorre antes dos 80 anos. A expectativa de vida tem aumentado para ambos os sexos no Brasil e em todo o mundo, porém em uma velocidade maior para homens do que para mulheres. Esta Diretriz foi baseada em uma revisão sistemática da literatura com relação a prevalência, etiologia, diagnóstico e tratamento da osteoporose em homens.
Osteoporosis, a metabolic disease characterized by low bone mass, deterioration of the bone tissue microarchitecture and increased susceptibility to fractures, is commonly regarded as a women's health problem. This point of view is based on the fact that compared with men, women have lower bone mineral density and longer lifespans and lose bone mass faster, especially after menopause, due to a marked decrease in serum estrogen levels. However, in the last 20 years, osteoporosis in men has become recognized as a public health problem due to the occurrence of an increasingly higher number of fragility fractures. Approximately 30% of all hip fractures occur in men. Recent studies show that the probability of fracture due to hip, vertebral or wrist fragility in Caucasian men older than fifty years, for the rest of their lives, is approximately 13% versus a 40% probability of fragility fractures in women. Men show bone mass loss and fractures later than women. Although older men have a higher risk of fracture, approximately half of all hip fractures occur before the age of 80. Life expectancy is increasing for both sexes in Brazil and worldwide, albeit at a higher rate for men than for women. This Guideline was based on a systematic review of the literature on the prevalence, etiology, diagnosis and treatment of osteoporosis in men.
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Citation Excerpt :
This finding indicates that early diagnosis and treatment of CTIBL is needed in the Korean clinical setting. The prevalence of osteoporosis in prostate cancer patients receiving ADT (17.3%) was somewhat higher in the present study than in two Japanese studies (range, 8.6%–12.1%) (Wang et al., 2008; Yuasa et al., 2010) but lower than that studies in western countries (range, 26.9%–42.9%) (Bruder et al., 2006; Morote et al., 2007; Morrison et al., 2011; Wei et al., 1999). The mechanisms are not clear, but the differences could be due to differences in genetics, treatments, or lifestyle factors (Morrison et al., 2011; Wang et al., 2008).
This study aimed to examine bone health status, identify factors associated with bone mineral density (BMD), and determine potential risk factors for osteoporosis in Korean prostate cancer patients receiving androgen deprivation therapy (ADT).
Using a cross-sectional descriptive design, we recruited 139 men with prostate cancer receiving ADT at two university-based hospitals in South Korea. Participants completed a self-reported questionnaire and underwent dual energy X-ray absorptiometry testing. BMD (gm/cm²), bone health status (normal BMD, osteopenia, and osteoporosis), and lifestyle variables (physical activity, smoking, and alcohol consumption) were measured.
The prevalence in our sample was 49.6% for osteopenia and 17.3% for osteoporosis. In multivariate linear regression analyses, BMD was positively associated with body mass index, number of comorbidities, and level of physical activity and negatively associated with being unemployed or retired, having a lower monthly income, and being treated with gonadotropin-releasing hormone therapy alone. In logistic regression analyses, potential risk factors for osteoporosis were low monthly income (OR = 4.33, p = 0.011), receipt of radiation therapy (OR = 4.69, p = 0.018), and lack of regular physical activity (OR = 2.63, p = 0.035).
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Rapid CommunicationsAndrogen deprivation therapy for prostate cancer results in significant loss of bone density

Abstract

Section snippets

Subjects

Clinical and demographic characteristics

Comment

Urol Clin North Am

J Urol

J Urol

Urology

J Urol

J Urol

Cancer statistics, 1999

CA Cancer J Clin

The National Cancer Data Base report on race, age, and region variations in prostate cancer treatment

Cancer

Rapid Communications
Androgen deprivation therapy for prostate cancer results in significant loss of bone density