Effects of oral clodronate on bone mineral density in patients with relapsing breast cancer.
The high prevalence of bone metastases in breast cancer and the risk that spinal and femoral osteoporosis may add further morbidity provide a rationale for bisphosphonate therapy in patients with skeletal metastases from mammary carcinoma. We investigated the effects of oral clodronate given during 9 months, with a 24-month follow-up, on bone mineral density (BMD), on biochemical markers of bone remodeling, and on osseous complications in 67 women with documented relapsing breast cancer, aged 58.7 +/- 1.5 years (x +/- SEM). Patients with active cancer disease were randomly allocated to two groups, with or without clodronate treatment (1600 mg/day, orally). Twenty-six women considered in complete remission (52.4 +/- 2.4 years) were also studied. Expressed in deviation from gender- and age-matched normals (z score), base-line BMD at the levels of lumbar spine (LS), femoral neck (FN), and midfemoral shaft (FS) was +0.10 +/- 0.22 vs. -0.12 +/- 0.25, +0.03 +/- 0.19 vs. -0.54 +/- 0.24, and +0.08 +/- 0.14 vs. -0.02 +/- 0.22, in patients with active breast cancer and in subjects in remission, respectively. After 9 months of treatment, fasting urinary calcium to creatinine ratio was lower (0.26 +/- 0.04 vs. 0.40 +/- 0.04 mmol/mmol creatinine, p < 0.02) and serum osteocalcin was stabilized (-2.1 +/- 1.1 vs. +7.0 +/- 3.3 micrograms/L, as compared with pretreatment values, p < 0.02), in the clodronate-treated group. The rate of osseous complications (pathological fracture, hypercalcemic episode, scintigraphic or radiological evidence of metastasis development, chemo- or radiotherapy for bone disease progression) was 28.8 events per 100 patient-year in the clodronate-treated group vs. 39.0 in controls, and 31.5 vs. 40.5, after 9 and 15 months of follow-up, respectively. In 15 women without evident LS bone metastasis (7 clodronate-treated and 8 controls), LS BMD increased in the clodronate-treated group by +5.2 +/- 2.5% vs. -0.3 +/- 1.4%, and +8.1 +/- 4.7 vs. -0.9 +/- 1.7, after 10.3 +/- 0.4 and 17.3 +/- 1.2 months, respectively (p < 0.01), as compared with pretreatment values. These results indicate that clodronate treatment decreased bone turnover and attenuated cancer-related bone morbidity. In addition, clodronate increased LS BMD in apparently unaffected bone of women with relapsing breast cancer.
Rizzoli
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Division of Clinical Pathophysiology, World Health Organization Collaborating Center for Osteoporosis and Bone Disease, Geneva, Switzerland. rizzoli@cmu.unige.ch
Forni
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Schaad
M A
MA
Slosman
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Sappino
A P
AP
Garcia
J
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Bonjour
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JP
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D004002:Clodronic Acid / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005272:Femur Neck / Q000502:physiology; D005500:Follow-Up Studies; D006801:Humans; D008159:Lumbar Vertebrae / Q000502:physiology; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local
D018712:Analgesics, Non-Narcotic; D015415:Biomarkers; D004002:Clodronic Acid