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Effect of Once-Weekly Oral Alendronate on Bone Loss in Men Receiving Androgen Deprivation Therapy for Prostate Cancer: A Randomized Trial

Susan L. Greenspan, MD; Joel B. Nelson, MD; Donald L. Trump, MD; and Neil M. Resnick, MD
[+] Article and Author Information

From the University of Pittsburgh, Pittsburgh, Pennsylvania, and Roswell Park Cancer Institute, Buffalo, New York.


Acknowledgments: The authors thank the nursing, professional, laboratory, dietary, administrative, and study staff of the General Clinical Research Center and Osteoporosis Prevention and Treatment Center at the University of Pittsburgh and the members of the data and safety monitoring board for their oversight of the study.

Grant Support: In part by the National Institutes of Health (R01 DK61536), the National Institute of Diabetes and Digestive and Kidney Diseases (K24 DK062895), and the General Clinical Research Center of the University of Pittsburgh by the National Institutes of Health and the National Center for Research Resources (M01-RR00056).

Potential Financial Conflicts of Interest: Consultancies: S.L. Greenspan (Merck & Co. Inc.); Honoraria: S.L. Greenspan (Merck & Co. Inc.); Grants received: S.L. Greenspan (Merck & Co. Inc.).

Requests for Single Reprints: Megan Miller, 3471 Fifth Avenue, Suite 1110, Kaufmann Medical Building, Pittsburgh, PA 15213; e-mail, millerm@dom.pitt.edu.

Current Author Addresses: Dr. Greenspan: University of Pittsburgh, 3471 Fifth Avenue, Suite 1110, Pittsburgh, PA 15213-3221.

Dr. Nelson: Department of Urology, University of Pittsburgh, 5200 Center Avenue, Suite 209, Pittsburgh, PA 15232.

Dr. Trump: Roswell Park Cancer Institute, Elm and Carlson Streets, Buffalo, NY 14263.

Dr. Resnick: Division of Geriatric Medicine, University of Pittsburgh, Kaufmann Suite 500, 3471 Fifth Avenue, Pittsburgh, PA 15213.

Author Contributions: Conception and design: S.L. Greenspan, N.M. Resnick.

Analysis and interpretation of the data: S.L. Greenspan.

Drafting of the article: S.L. Greenspan.

Critical revision of the article for important intellectual content: S.L. Greenspan, J.B. Nelson, D.L. Trump, N.M. Resnick.

Final approval of the article: S.L. Greenspan, J.B. Nelson, D.L. Trump, N.M. Resnick.

Provision of study materials or patients: S.L. Greenspan, J.B. Nelson, D.L. Trump, N.M. Resnick.

Obtaining of funding: S.L. Greenspan, N.M. Resnick.

Administrative, technical, or logistic support: S.L. Greenspan.

Collection and assembly of data: S.L. Greenspan.


Ann Intern Med. 2007;146(6):416-424. doi:10.7326/0003-4819-146-6-200703200-00006
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Most baseline characteristics did not differ statistically significantly between the active treatment and placebo groups (Table 1). Ninety-six percent of the participants were white, with no substantial racial differences between groups. The median total daily intake of calcium (dietary plus supplements) was 874 mg/d (interquartile range, 534 to 1526 mg/d), and the mean total vitamin D intake was 562 U/d (95% CI, 489 to 635 U/d). At baseline, 59% of participants received gonadotropin-releasing hormone agonists, 2% received antiandrogen monotherapy, and 39% received a combination of these therapies (Table 1). Two men had orchiectomy before starting ADT therapy and both were in the placebo group. Men had been receiving ADT for a median of 14 months. Baseline levels of serum calcium, albumin, hematocrit, 25-hydroxyvitamin D, and parathyroid hormone were within the normal ranges. Baseline levels of total testosterone were in the castrate range and did not statistically significantly differ between the groups. Prostate-specific antigen levels were similar between groups.

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Figure 1.
Study flow diagram.

*Included 3 patients with elevated testosterone levels, 1 with elevated prostate-specific antigen level, 1 with metastatic bone tumors, 1 with recent history of renal-cell cancer, 1 receiving glucocorticoids, 1 with several active illnesses, and 1 receiving advice from a physician for a history of cardiovascular disease. † Included 1 patient with personal reasons, 1 patient concerned about gastrointestinal side effects, and 1 patient who was lost to follow-up before randomization. ‡ Included 1 patient with atrial fibrillation, 1 with metastatic bone tumors with initiation of intravenous bisphosphonates, and 1 patient with several medical problems. § Included 1 patient with cardiovascular and respiratory disease.

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Figure 2.
Mean (±SE) observed percentage change in bone mineral density from baseline to 6 and 12 months.

The between-group differences in percentage points at 6 and 12 months were 4.0 (CI, 2.6 to 5.4) and 5.1 (CI, 3.5 to 6.7) for posterior–anterior spine, respectively; 4.3 (CI, 2.0 to 6.6) and 5.6 (CI, 2.5 to 8.6) for lateral spine, respectively; 0.5 (CI, −0.5 to 1.5) and 1.4 (CI, 0.5 to 2.4) for total hip, respectively; 1.0 (CI, −0.5 to 2.4) and 2.3 (CI, 1.0 to 3.7) for femoral neck, respectively; 0.3 (CI, −1.0 to 1.6) and 0.8 (CI, −0.4 to 2.1) for one-third distal radius, respectively; and 0.8 (CI, −0.5 to 2.1) and 1.4 (CI, 0.2 to 2.6) for ultra distal radius, respectively. *P < 0.01 changes from baseline using paired t-test. †P < 0.01 for comparison between alendronate and placebo groups using unpaired t-test. ‡P < 0.05 for changes from baseline using paired t-test. §P < 0.05 for comparison between alendronate and placebo groups using unpaired t-test.

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Figure 3.
Mean (±SE) percentage change in markers of bone turnover from baseline to 6 and 12 months.

The between-group differences in percentage points at 6 and 12 months were −44.1 (CI, −59.0 to −29.3) and −60.4 (CI, −83.8 to −36.9) for urinary N-telopeptide crosslinks of type I collagen (NTX), respectively; −52.6 (CI, −73.1 to −32.0) and −56.8 (CI, −80.5 to −33.1) for serum C-telopeptide crosslinks of type I collagen (CTX), respectively; −66.3 (CI, −92.2 to −40.3) and −60.2 (CI, −83.1 to −37.2) for N-terminal propeptide of type I procollagen (P1NP), respectively; and −24.7 (CI, −38.4 to −11.0) and −27.0 (CI, −39.4 to −14.6) for osteocalcin, respectively. *P < 0.01 for changes from baseline. †P < 0.01 for comparison between alendronate and placebo groups. ‡P < 0.05 for changes from baseline.

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Andropause and Osteoporosis
Posted on March 31, 2007
Harry L. Gale
YRMC
Conflict of Interest: None Declared

Too little attention is paid to the rapid bone loss that can occur as a result of decreases in androgen production seen in men that may result from ageing or the hormone manipulation used to deprive prostate cancer cells.Peripheral testosterone conversion to estrogen still maintains the boney matrix in males as in the female. My first osteoporotic patient treated with alendronate 8 years ago was a male and presented with lumbar compression fractures. These proved refractory to alendronate and calcitonin with continued fractures. He eventually was felt to have low total and free serum testosterone levels as the cause of his ongoing fractures. This patient has been treated with IM testosterone for the past 3 years and has remained fracture free. Men should recieve timely DXA screening and a metabolic workup that includes a testosterone level. Certainly, those who have had deprivation therapy for prostate cancer will need a baseline screen since they are likely to suffer the same rapid bone loss phase seen in women at menopause.

Conflict of Interest:

None declared

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Summary for Patients

Preventing Bone Loss in Men with Prostate Cancer

The summary below is from the full report titled “Effect of Once-Weekly Oral Alendronate on Bone Loss in Men Receiving Androgen Deprivation Therapy for Prostate Cancer. A Randomized Trial.” It is in the 20 March 2007 issue of Annals of Internal Medicine (volume 146, pages 416-424). The authors are S.L. Greenspan, J.B. Nelson, D.L. Trump, and N.M. Resnick.

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