Bone Health in Patients Receiving Aromatase Inhibitors

Introduction to Bone Health

The American Society of Clinical Oncology (ASCO) recommends that all patients receiving aromatase inhibitors, such as exemestane, should be encouraged to exercise regularly and take adequate calcium and vitamin D supplements 1

Exemestane is associated with a significant loss of bone mineral density (BMD) despite supplementation with calcium and vitamin D 2
Patients with moderate BMD loss who receive exemestane should be considered for the use of bone-protecting agents such as bisphosphonates and RANKL inhibitors 1

A history of osteoporosis and/or severe bone loss is a relative contraindication for the use of exemestane 1

Before initiating aromatase inhibitor therapy, physicians should evaluate the patient's baseline fracture risk and measure bone mineral density 1
Bone mineral density testing should be performed every 1-2 years to monitor response to therapy, and repeat DXA scan every two years for patients with osteopenia, as recommended by the American College of Rheumatology, the National Osteoporosis Foundation, and supported by 3, 4, 5

Exercise with weight-bearing activities is recommended for bone health 6
Smoking cessation and limiting alcohol consumption are beneficial for bone health, as recommended by the American College of Clinical Oncology 7, 6
Regular weight-bearing exercise helps prevent bone loss, and regular assessment of lifestyle habits, including avoidance of tobacco and limitation of alcohol consumption, is recommended for maintaining bone health, as supported by 6, 8, 9

Vitamin D supplementation is recommended for patients with 25-hydroxyvitamin D levels below 30 ng/mL, as suggested by the American Journal of Kidney Diseases 10
The American Gastroenterological Association recommends pairing calcium with vitamin D supplementation, with 800-1000 IU of vitamin D daily, and notes that vitamin D3 (cholecalciferol) is preferred over vitamin D2 11, 7, 8, 9, 3
Calcium supplementation is recommended for optimal bone health, with a daily intake of 1000-1200 mg of calcium, as supported by the National Osteoporosis Foundation, American College of Clinical Oncology, and National Institutes of Health (NIH) 7, 8, 9, 3
Daily calcium intake recommendations vary by population:
Population Recommended Daily Calcium Intake
Postmenopausal women 1200 mg
Premenopausal adults (19-50 years) 1000 mg
Men over 70 years 1200 mg
The Gastroenterology society recommends elemental calcium intake of 1000 mg/day for men and pre-menopausal women, and 1500 mg/day for men and women over 50 years old 13
Patients with severe vitamin D deficiency (<10 ng/ml) may require higher doses (4000-5000 UI daily) for 2 months to achieve optimal levels, as recommended by Clinical Nutrition guidelines 14
Adults over 50 years should take 800-1000 IU/day of vitamin D, and patients with osteopenia should receive daily supplementation of 800-1000 IU of vitamin D and 1000-1200 mg of calcium, as recommended by the National Institutes of Health (NIH) and supported by 3, 8, 9

Population	Recommended Daily Calcium Intake
Postmenopausal women	1200 mg
Premenopausal adults (19-50 years)	1000 mg
Men over 70 years	1200 mg

For patients with established osteoporosis or at high risk, pharmacologic therapy with bisphosphonates as the first-line treatment is recommended, with calcium and vitamin D as essential components of any osteoporosis treatment regimen, supported by the American Academy of Family Physicians and the National Osteoporosis Foundation 15, 13, 16
Teriparatide (Forteo) is typically recommended for severe osteoporosis, as it is more effective for patients with severe disease or who have had fractures, according to the American Academy of Family Physicians and the National Osteoporosis Foundation 16, 4

Regular assessment of serum calcium levels and renal function is recommended for patients taking calcium supplements, as recommended by the American Gastroenterological Association and the National Comprehensive Cancer Network guidelines 17, 8
The National Osteoporosis Foundation and American Society for Preventive Cardiology state that there is moderate-quality evidence that calcium with or without vitamin D intake from food or supplements has no relationship to cardiovascular disease risk in generally healthy adults 18
Calcium intake from food and supplements that does not exceed the tolerable upper level of intake (2000-2500 mg/day) should be considered safe from a cardiovascular standpoint 18