Osteoporosis: Howell A

Reid DM, Doughty J, Eastell R, Heys SD, Howell A, McCloskey EV, Powles T, Selby P, Coleman RE. · Department of Rheumatology, University of Aberdeen, United Kingdom. · Cancer Treat Rev. · Pubmed #18515009 No free full text.

Abstract: In postmenopausal women, the use of aromatase inhibitors increases bone turnover and induces bone loss at sites rich in trabecular bone at an average rate of 1-3% per year leading to an increase in fracture incidence compared to that seen during tamoxifen use. The bone loss is much more marked in young women with treatment-induced ovarian suppression followed by aromatase inhibitor therapy (average 7-8% per annum). Pre-treatment with tamoxifen for 2-5 years may reduce the clinical significance of the adverse bone effects associated with aromatase inhibitors, particularly if this leads to a shortening in the duration of exposure to an aromatase inhibitor. However, skeletal status should still be assessed at the commencement of aromatase inhibitor therapy. The rate of bone loss in women who experience a premature menopause before the age of 45 or are receiving ovarian suppression therapy is accelerated by the concomitant use of aromatase inhibitors. These patients are considered to be at high risk of clinically important bone loss and should have a baseline dual energy X-ray absorptiometry (DXA) assessment of bone mineral density (BMD). Randomised clinical trials in postmenopausal women indicate that bisphosphonates prevent the bone loss and accelerated bone turnover associated with aromatase inhibitor therapy and are a promising strategy for the prevention and treatment of osteoporosis in this setting. Treatment initiation recommendations are based on a combination of risk factors for osteoporotic fracture and BMD levels. Bisphosphonates, along with a healthy lifestyle and adequate intake of calcium and vitamin D are the treatments of choice to prevent bone loss. Due to the rate of bone loss associated with breast cancer treatments, and uncertainties about the interaction between aromatase inhibitor use and BMD for fracture risk, the threshold for intervention has been set at a higher level than that generally recommended for postmenopausal osteoporosis. Management recommendations have been summarised in two algorithms, one for women experiencing a premature menopause and the other for postmenopausal women requiring adjuvant aromatase inhibitor therapy.

Warren R, Harvie M, Howell A. · Addenbrooke's Hospital, Cambridge, UK. · Treat Endocrinol. · Pubmed #15330677 No free full text.

Abstract: Postmenopausal women in Western societies are conscious of breast cancer as a potential cause of death and ill health, which they wish to avoid with the advice of their doctors. Yet many factors that predispose women to the development of cancer will have been laid down before the menopause, in their genetic makeup or during their adolescent years. Even in middle age it is important to take account of the intrinsic level of risk, and to give women advice tailored to their own individual risk level. This results from their family history, previous diseases such as benign breast disease, and previous treatment for breast cancer or Hodgkin's disease. For those at the highest level of risk, strategies will include regular screening, prophylactic mastectomy, and the use of chemoprevention agents, such as tamoxifen. These women should avoid hormone replacement therapy (HRT) and control their menopausal symptoms and osteoporosis through the use of other agents now available - venlafaxine for menopausal symptoms and bisphosphonates for osteoporosis. Raloxifene is an agent under trial that may be valuable for breast cancer control as well as for osteoporosis. Women at standard population risk will require less robust preventive strategies, which will include screening and lifestyle modification. Their decisions regarding HRT should now be modified by recent evidence of associated risks. Recent studies show that tibolone causes less mammographic density and has a lower relative risk of breast cancer than combined estrogen/progestogen preparations. There is limited evidence that controlling obesity, participating in exercise and adopting a diet low in fats and high in fruit and vegetables will alter risk at this age. These precautions will, however, reduce the risk of other diseases common in this age group, such as hypertension, heart disease, stroke, and type 2 diabetes mellitus. Alcohol, even in small amounts, is a risk factor for breast cancer. Given the cardioprotective effect of moderate alcohol intake, advice on alcohol must reflect the individual relative risk of cardiovascular disease and breast cancer.Personal risk assessment is relevant for all women. Screening and a healthy lifestyle are worthwhile approaches for all, with the more aggressive approaches such as chemoprevention and prophylactic surgery reserved for those who have substantially elevated levels of risk. Once the menopause has passed, screening is probably the most effective evidence-based tool for breast cancer control by early diagnosis.

Walls J, Assiri A, Howell A, Rogers E, Ratcliffe WA, Eastell R, Bundred NJ. · Department of Surgery, University Hospital of South Manchester, UK. · Br J Cancer. · Pubmed #10376982 No free full text.

Abstract: Objective assessment of response in bone metastases from breast cancer using radiological techniques takes up to 6 months of treatment to be certain of a response, and sclerotic metastases are not evaluable. Standard serum and urinary tumour markers may not always be utilized to predict response, as they may not be elevated, and therefore may not change on treatment. The development of the urinary pyridinoline cross-link assays which measure mature bone breakdown products have been shown to be highly sensitive and specific as a measure of bone change in osteoporosis. We have measured pyridinoline (Pyr) and deoxypyridinoline (Dpyr) cross-links sequentially in 36 breast cancer patients with bone metastases, to determine if the measurement of these analytes predicts response at an earlier stage than radiological assessment. Response was assessed by UICC criteria. Seventeen women responded to hormonal therapy, whilst 19 developed progressive disease. Both Pyr and Dpyr increased sequentially in women with progressive disease with changes becoming apparent by 8 weeks (P<0.03). In responding women, cross-link levels did not change significantly. Pyr and Dpyr were more sensitive and specific than the standard serum tumour marker CA 15-3. Urinary cross-link measurements provide a novel objective method of assessing response to treatment in women with bone metastases. Initial elevated urinary cross-link markers identify patients who tend not to respond to changes in hormonal therapy.