Role of Low Levels of Endogenous Estrogen in Regulation of Bone Resorption in Late Postmenopausal Women

Heshmati, H. M.; Khosla, Sundeep; Robins, Simon P.; O’Fallon, W. Michael; Melton, L. Joseph; Riggs, B. Lawrence

doi:10.1359/jbmr.2002.17.1.172

Cited by 185 publications

(76 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…That mineralisation was significantly less than the control group is interesting. Although selective-estrogen receptor downregulators, such as fulvestrant, are reported to lack estrogen agonist activity, results of preclinical studies have shown that fulvestrant may actually have agonist and antagonist effects on bone, depending on the presence of circulating estradiol levels [58]. In ovariectomized rats, bone turnover and bone loss increased after fulvestrant therapy, whereas bone turnover and bone loss decreased in rats with intact ovaries receiving fulvestrant [53].…”

Section: Discussionmentioning

confidence: 99%

Estrogen Plus Estrogen Receptor Antagonists Alter Mineral Production by Osteoblasts In Vitro

2011

View full text Add to dashboard Cite

ing in a decrease in whole bone and tissue biomechanical properties [ 5-9 ]. Interestingly, although osteoporosis reduces bone mass and structural strength, a recent study found that the remaining bone tissue is signifi cantly stronger and stiff er [ 10 ]. This unexpected fi nding has been corroborated to some extent by micro-CT studies which demonstrated an increase in the tissuelevel mineral content which was counter to the overall reduction in bone mineral density owing to a loss of bone mass [ 10 ]. More recent studies have provided further evidence of an increase in tissue mineral during osteoporosis [ 11 , 12 ]. Such changes may occur to compensate for bone loss, or alternatively these changes may occur prior to bone resorption and be causative. However, although it is intriguing to speculate on such events, it remains that the mechanisms by which an increase in mineralisation is initiated are unknown.

show abstract

Section: Discussionmentioning

confidence: 99%

Estrogen Plus Estrogen Receptor Antagonists Alter Mineral Production by Osteoblasts In Vitro

2011

View full text Add to dashboard Cite

show abstract

“…Comparative clinical trials with tamoxifen demonstrate the superiority of aromatase inhibitors in length of disease progression and survival (Bonneterre et al 2000, Mouridsen et al 2003, Nabholtz et al 2003. However as compared with tamoxifen, aromatase inhibitors resulted in increased bone resorption (Heshmati et al 2002) and fracture risk (Howell et al 2005).…”

Section: Treatment Of Metastatic Bone Disease Hormone Therapiesmentioning

confidence: 99%

Hypercalcaemia of malignancy and basic research on mechanisms responsible for osteolytic and osteoblastic metastasis to bone

Clines

Guise²

2005

Endocr Relat Cancer

230

211

View full text Add to dashboard Cite

Calcium homeostasis is a tightly regulated process involving the co-ordinated efforts of the skeleton, kidney, parathyroid glands and intestine. Neoplasms can alter this homeostasis indirectly through the production of endocrine factors resulting in humoral hypercalcaemia of malignancy. Relatively common with breast and lung cancer, this paraneoplastic condition is most often due to tumour production of parathyroid hormone-related protein and ensuing increased osteoclastic bone resorption. Although control of hypercalcaemia is generally successful, the development of this complication is associated with a poor prognosis. The metastasis of tumour cells to bone represents another skeletal complication of malignancy. As explained in the 'seed and soil' hypothesis, bone represents a fertile ground for cancer cells to flourish. The molecular mechanisms of this mutually beneficial relationship between bone and cancer cells are beginning to be understood. In the case of osteolytic bone disease, tumour-produced parathyroid hormone-related protein stimulates osteoclasts that in turn secrete tumour-activating transforming growth factor-b that further stimulates local cancer cells. This 'vicious cycle' of bone metastases represents reciprocal bone/ cancer cellular signals that likely modulate osteoblastic bone metastatic lesions as well. The development of targeted therapies to either block initial cancer cell chemotaxis, invasion and adhesion or to break the 'vicious cycle' is dependent on a more complete understanding of bone metastases. Although bisphosphonates delay progression of skeletal metastases, it is clear that more effective therapies are needed. Cancer-associated bone morbidity remains a major public health problem, and to improve therapy and prevention it is important to understand the pathophysiology of the effects of cancer on bone. This review will detail scientific advances regarding this area.

show abstract

“…Studies in ovariectomized rats showed that LET had no effect on serum lipids [73]. Short courses of therapy with LET (3 and 6 months) also had no significant effect on serum lipids (total, high-density lipoprotein [HDL], or low-density lipoprotein [LDL] cholesterol) [74,75]. In the MA.17 trial, hypercholesterolemia (16% versus 16%; p = .79) and cardiovascular events (5.8% for LET versus 5.6% for TAM; p = .76) occurred with a similar frequency in patients treated with LET and patients receiving placebo following 5 years of TAM therapy [22].…”

Section: Ais and Cvdmentioning

confidence: 99%

Appraising Adjuvant Aromatase Inhibitor Therapy

Perez

2006

The Oncologist

View full text Add to dashboard Cite

Tamoxifen, once the gold standard adjuvant endocrine therapy for early breast cancer, is being challenged by third-generation aromatase inhibitors (AIs) that have demonstrated improved disease-free survival in a variety of adjuvant settings for early breast cancer. Tamoxifen and AIs have different safety profiles, which should allow physicians to begin to individualize treatment based on a patient's comorbidities and risk factors. Because of its properties as a partial estrogen agonist, tamoxifen has a positive effect on serum lipids and may confer a cardioprotective benefit, as well as a beneficial effect on bone health. However, tamoxifen increases the risk for endometrial cancer and cerebrovascular/thromboembolic events. In comparison, the major side effect of AIs is increased bone loss, which may heighten the risk for osteoporotic fractures and bone pain. Because of their superior efficacy and manageable side effects, AIs are a cost-effective alternative to tamoxifen, and clinical guidelines now embrace AIs as appropriate adjuvant therapy for hormone-sensitive early breast cancer. The anticipated results of ongoing trials will provide further insights into the long-term safety and application of AI therapy in the adjuvant setting.

show abstract

Role of Low Levels of Endogenous Estrogen in Regulation of Bone Resorption in Late Postmenopausal Women

Cited by 185 publications

References 30 publications

Estrogen Plus Estrogen Receptor Antagonists Alter Mineral Production by Osteoblasts In Vitro

Estrogen Plus Estrogen Receptor Antagonists Alter Mineral Production by Osteoblasts In Vitro

Hypercalcaemia of malignancy and basic research on mechanisms responsible for osteolytic and osteoblastic metastasis to bone

Appraising Adjuvant Aromatase Inhibitor Therapy

Contact Info

Product

Resources

About