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Old 03-01-2011, 01:13 PM   #1
Hopeful
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Cancer Therapy Associated Bone Loss: Implications for Hip Fractures in Mid-Life Women

Clin Cancer Res. 2011 Feb 15;17(4):560-568, BJ Edwards, DW Raisch, V Shankaran, JM McKoy, W Gradishar, AD Bunta, AT Samaras, SN Boyle, CL Bennett, DP West, TA Guise

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Middle-aged breast cancer survivors suffer hip fractures at an earlier age than do patients without breast cancer, according to case reports and epidemiologic studies.

SUMMARY

OncologySTAT Editorial Team


About one-quarter of breast cancer cases occur in premenopausal women. Because these women often have chemotherapy-induced menopause and receive adjuvant hormonal therapies, they may suffer accelerated bone loss and subsequent fractures. Edwards et al evaluated the occurrence and functional impact of hip fractures in menopausal women with early-stage breast cancer, including case reports of hip fractures and a review of the literature.

The researchers identified 6 patients with breast cancer who had a hip fracture between the ages of 25 and 60 years and were seen at the Bone Health and Osteoporosis Center at Northwestern University, Chicago, from 2005 to 2007. In addition to physical examination, patients had bone densitometry, prefracture functional assessment, and evaluation for secondary causes of bone loss. The physical examination and functional assessment were repeated at 12 months.

Of the 6 patients, 5 had osteopenia and 1had osteoporosis; 2 had vitamin D deficiency and low calcium absorption, and 1 had vitamin D deficiency with high urinary calcium loss. Median age of the patients was 53.5 years. Median age at the time of diagnosis and chemotherapy-induced menopause was 48 years. Fractures developed 1 to 4 years after the cancer diagnosis. Of the 6 patients, 4 were estrogen–receptor (ER-) positive and had received aromatase inhibitors (AIs), which may contribute to the occurrence of hip fractures.

Before sustaining their hip fractures, none of the study participants reported difficulty in performing activities of daily living. At the assessment 12 months after the hip fracture, there was a clinically important functional decline. The women had the greatest difficulty in doing heavy housework, climbing stairs, and shopping, and 2 women reported difficulty walking more than 200 yards.

Using the US Food and Drug Administration’s Adverse Events Reporting System (FDA AERS), from 1998 to 2008, the researchers identified 226 cases of fractures associated with chemotherapy and/or AIs. Among the women 64 years of age or younger, there were 78 fractures, including 15 hip and femur fractures. A total of 149 cases (65%) were associated with the use of AIs.

Finally, the researchers searched the literature for studies involving adverse bone effects associated with cancer therapy. A claims-based case-control study showed that survivors of breast cancer who received AIs had more fractures than those who did not receive AIs. The Women’s Health Initiative showed an increased risk for fractures among survivors of breast cancer compared with age-matched women without breast cancer. Several trials have shown that upfront use of the bisphosphonate zoledronic acid increases bone mineral density (BMD) in women receiving AIs and reduces fracture risks.

The authors concluded that hip fractures in survivors of breast cancer occur at an earlier age and at a higher BMD than hip fractures in patients with postmenopausal osteoporosis. In women who survive breast cancer, hip fractures can occur as early as the sixth decade of life, compared with occurrence in the eighth decade in patients with osteoporosis. In this study, 5 of the 6 women with breast cancer who had hip fractures had osteopenia, but current guidelines do not recommend osteoporosis therapy for these patients.

The clinical trials suggest that all three of the third-generation AIs affect bone turnover and BMD, leading to an increased fracture risk. The AIs are highly effective and are in widespread use as adjuvant therapy in patients with ER-positive early breast cancer. As the number of survivors of cancer increases, reducing the risks of AI-associated bone loss becomes more critical, especially in younger patients who have longer survival.

In light of the significant functional decline associated with hip fractures, the authors urged that future studies evaluate the current intervention thresholds for treatment of osteoporosis and use of bisphosphonates in patients taking AIs.

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