Introduction
Pathophysiology of osteoporosis in cancer patients
Non-modifiable risk factors | |
Age | Personal history of previous fracture |
Female sex | Genetic (family history) |
Ethnicity (Asian or Caucasian) | Hip fractures in first-degree relatives |
Modifiable risk factors | |
Low levels of physical activity (prolonged immobilization and/or sedentary lifestyle) | Estrogen deficiency (early menopause, prolonged amenorrhea periods) |
Smoking | Low calcium intake or malnutrition |
Alcohol consumption (≥ 3 units per day) | Osteoporosis secondary to chronic or consumptive diseases |
Low weight (< 58 kg or 127 lb) | Chronic glucocorticoid use |
Drugs used in oncology | |
Aromatase inhibitors (BC) | Chemotherapy |
Steroidal (exemestane) | Alkylating agents |
Non-steroidal (anastrozole, letrozole) | Anthracyclines Docetaxel |
GnRH agonists (BC: goserelin, triptorelin) | Doxorrubicin |
Selective ER Modulators (BC) | 5-fluorouracil |
Androgen deprivation therapy (PC) | Other |
LHRH analogues (goserelin, buserelin, leuprorelin, triptorelin) | Other drugs |
LHRH antagonists (goserelin) | Antidepressants and serotonin reuptake inhibitors |
Antiandrogens (enzalutamide, bicalutamide, flutamide, nilutamide) | Oral antidiabetics (thiazolidinediones) |
Other osteopenizing drugs | |
Methotrexate | NSAIDs |
Megestrol acetate | Estramustine |
Platinum compounds | Ifosfamide |
Cyclophosphamide | Radiotherapy |
Interferon-alfa | Combination of chemotherapy regimens |
Cyclosporine | Valproic acid |
Vitamin A |
General risk factors for osteoporosis
Non-modifiable risk factors
Modifiable risk factors
Specific risk factors for osteoporosis
Breast cancer
Prostate cancer
Other tumors
Diagnosis and monitoring of osteoporosis in cancer patients
Role of bone biomarkers in treatment monitoring and evaluation
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Bone formation markers (BFMs), which derive from formation processes and reflect osteoblastic activity: alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP), procollagen type I carboxy-(PICP) and amino-terminal propeptides (PINP), and osteocalcin.
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Bone resorption markers (BRMs), which derive from the resorption processes and reflect osteoclastic activity: cross-linked carboxy- and amino-terminal telopeptides of type I collagen (CTX and NTX), tartrate-resistant acid phosphatase (TRAP), pyridinolines and deoxypyridinolines, hydroxyproline and sialoprotein.
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BRMs measure functional activity and do not quantify bone mass, so they should not be used for the diagnosis of osteoporosis.
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Collagen-dependent BRMs may be altered due to non-bone pathologies, such as chronic liver disease of any origin.
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BALP may be altered depending on the liver ALP values.
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Chronic renal failure may alter the concentration of BRMs.
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Bone fractures may alter BRM values for several months.
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In general, it is preferable to measure BRMs in serum instead of in urine, due to their lower variability.
Diagnostic and monitoring tests: recommendations and frequency
Patient assessment | Comments | |
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Medical history | Fracture history | Previous fractures increase the risk of future fractures, regardless of BMD. It is useful to perform a spinal x-ray before starting treatment in order to detect previous asymptomatic fractures. Techniques such as CT, MRI and/or PET can be very useful in determining whether an acute fracture is a bone metastasis |
Classic risk factors | Family history of osteoporosis should be included. The FRAX® is an easily reproducible diagnostic tool developed by the University of Sheffield from a meta-analysis of a wide variety of risk factors for osteoporotic fractures (https://www.sheffield.ac.uk/FRAX/). It allows the estimation of the 10-year risk of hip fracture and major osteoporotic fracture, with or without concomitant determination of BMD, although it may underestimate the risk in cancer patients. When using the FRAX® tool in cancer patients, cancer can be considered a “secondary osteoporosis”. One limitation is that this tool does not weigh the number, severity, or location of previous fractures, or the total or cumulative GC treatment | |
Medications | Treatment review for potentially osteopenizing drugs | |
Fall risk estimation | Estimation of fall risk | |
Vitamin D | Vitamin D deficiency is an independent risk factor for low bone mass, falls, and fractures [112]. Determination of 25-hydroxyvitamin D levels allows patients to be classified as normal (> 30 ng/ml), insufficient (20–30 ng/ml) or deficient (< 20 ng/ml) | |
Physical & complementary examinations | Height | Height should be measured at least once a year and whenever there is suspicion of a new vertebral compression fracture |
BRMs | Variations throughout the day explain why their reproducibility is not a critical factor in the assessment of FR in cancer patients. However, it may be useful to determine BRMs at the beginning of diagnosis or once treatment has started to gain insight into the status of bone metabolism and, above all, to monitor treatment | |
BMD | DXA is recommended to measure and compare BMD with previous DXA to assess the progression of osteoporosis. The WHO recommends performing these measurements every 2 years from menopause. The standardized recommendation for menopausal women treated with AI was an annual BMD assessment for the duration of treatment, especially if there is baseline osteopenia or osteoporosis [113]. The ASCO recommends increasing the frequency of DXA follow-up screening if deemed medically necessary based on the results of BMD testing and expected bone loss [84] Fig. 2 |
Prevention and treatment of osteoporosis in cancer patients
Non-pharmacological measures | Pharmacological measures |
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Smoking cessation | Hormone replacement therapies |
Avoid excess alcohol intake | Antiresorptive agents |
Avoid excess caffeine intake | Selective estrogen receptor modulators (SERMs) |
Avoid sedentary lifestyle | Calcitonin |
Prevent falls | Bisphosphonates (alendronate, risedronate, ibandronate, zoledronate) |
Balanced diet | Denosumab (anti-RANKL biologic) |
Adequate intake of: | |
Trace minerals | |
Proteins | |
Vitamin D | |
Calcium Combination of calcium and vitamin D | |
Physical therapy (improve muscle strength and balance) |