Why Do Bone Fractures Occur in Cancer Patients?

What Is a Bone Fracture?

A bone fracture is a disruption of the bone's anatomical continuity. It occurs more frequently in cancer patients because of both direct tumor effects on the skeleton and side effects of cancer treatments on bone metabolism.

Why Do Bone Fractures Occur in Cancer Patients?

Metastatic Bone Disease (Osteolytic / Osteoblastic Lesions)

• Breast, prostate, lung, thyroid, and kidney cancers frequently metastasize to bone.
• Tumor cells settle in the bone microenvironment and alter osteoclastic (bone-destroying) or osteoblastic (bone-forming but structurally weak) activity.
• Bone tissue weakens particularly in osteolytic metastases, increasing pathological fracture risk.

Treatment-Related Bone Loss (Cancer-Related Osteoporosis)

• Chemotherapy, radiotherapy, endocrine treatments, and steroids can reduce bone mineral density (BMD):
• Aromatase inhibitors (e.g., anastrozole, letrozole, exemestane) cause bone loss by lowering estrogen in postmenopausal women.
• GnRH agonists (e.g., leuprolide, goserelin) increase bone resorption by suppressing sex hormones in both men and women.
• Glucocorticoids (used for >3 months) inhibit osteoblast activity while increasing osteoclast activity.
• Radiotherapy contributes to bone weakness by affecting osteocytes in the treated area.

Multiple Myeloma and Bone Loss

• Multiple myeloma cells stimulate osteoclast activity by increasing RANKL expression in bone marrow.
• This can cause widespread osteolytic lesions and spontaneous fractures (such as a femoral fracture simply while standing up).

What Does a Bone Fracture Look Like?

Symptoms of a bone fracture include:

• Severe pain
• Swelling
• A cracking sound at the moment of fracture
• Skin bruising or bleeding
• Limb deformity
• Loss of function in the fractured limb

Bone loss, however, is usually not visible to the naked eye. Your healthcare team may therefore order a test to measure bone density.

The most commonly used test is a DXA or DEXA scan (Dual-Energy X-Ray Absorptiometry). It is painless and easy to perform.

Who Is at Risk of Bone Fractures?

Women have a higher risk of bone fractures.

Fracture and bone loss risk increase in people over 50.

People who have undergone hematopoietic stem cell transplantation also have a higher risk.

Cancer treatments affecting hormone levels increase bone loss and thus fracture risk.

These treatments include:

• Chemotherapy (affecting the ovaries or testes)
• Treatments targeting hormone production

Examples of hormone treatments:

• Anastrozole (Arimidex)
• Exemestane (Aromasin)
• Letrozole (Femara)
• Goserelin (Zoladex)
• Leuprolide (Lupron)
• Triptorelin (Trelstar)

Targeted therapies may also increase bone loss. These include:

• Imatinib
• Nilotinib
• Dasatinib
• Ibrutinib

Steroids are used in some cancer treatments. ► Steroid use for longer than 3 months may increase bone fracture risk.

Diagnosis, Treatment, and Management

Diagnostic Methods

Bone fractures in cancer patients are diagnosed by assessing clinical signs and imaging together. The diagnostic process includes the following steps:

Clinical Assessment

• Sudden localized pain
• Restricted movement
• Deformity
• Swelling or tenderness
• Fracture during weight-bearing or after minimal trauma (suspected pathological fracture)

Imaging Methods

• Plain radiography (X-ray): Initial assessment of the fracture's presence, location, and extent.
• Computed Tomography (CT): Detailed anatomical assessment of the fracture line.
• Magnetic Resonance Imaging (MRI): Shows soft tissue involvement, nerve compression, and spinal cord involvement, particularly in vertebral compression fractures.
• Bone Scintigraphy: Used to screen for widespread metastatic involvement.
• PET/CT: Used for both diagnosis and oncological assessment in patients with bone metastases.
• DEXA (Dual Energy X-ray Absorptiometry): The gold standard for measuring bone mineral density.

Treatment Approach

Fracture treatment aims to control pain, restore function, enable mobilization, and preserve quality of life.

Medical Treatment

Pain control: Nonsteroidal anti-inflammatory drugs (NSAIDs), opioids

Bone-strengthening drugs:

• Bisphosphonates (zoledronic acid, pamidronate): Suppress osteoclast activity and reduce fracture risk
• Denosumab: RANKL inhibitor; preferred as an alternative to bisphosphonates, particularly in patients with renal impairment

Surgical and Interventional Procedures

• Orthopedic fixation: Plates/screws/nails for unstable long-bone fractures
• Vertebroplasty / Kyphoplasty: Stabilization with bone cement for painful vertebral compression fractures
• Tumor resection and reconstruction: Surgical removal of the lesion causing the pathological fracture

Fracture Management and Supportive Approaches

Rehabilitation and Mobilization

Early mobilization is critical to preventing complications after fracture (such as pressure ulcers, deep vein thrombosis, and pneumonia).

Physical therapy and rehabilitation programs aim to:

• Preserve or increase muscle mass and strength: Particularly in cancer patients with sarcopenia (muscle loss), resistance exercises (isotonic/isometric) support the musculoskeletal system, helping prevent further fractures.
• Improve balance and proprioception: Exercises targeting coordination between the vestibular system and lower-limb muscles reduce fall risk.
• Use assistive devices: After individualized assessment, walkers, canes, or orthopedic braces may be prescribed to support functional mobility. These devices allow safe movement and reduce weight-bearing.

Nutrition and Supplements

Optimal nutrition is fundamental to maintaining bone health. Because cancer patients have a high malnutrition risk, the following are important for preventing fractures and supporting healing:

Calcium and vitamin D supplementation:

• Calcium: 1000–1200 mg daily is recommended, preferably from dairy products, leafy green vegetables, and fortified foods.
• Vitamin D: 800–1000 IU/day is recommended. If serum 25(OH)D is <20 ng/mL, higher-dose replacement is needed.
• Vitamin D supports osteoblast activity by increasing intestinal calcium absorption and reduces fall risk by improving muscle function.

Adequate protein intake:

• Daily protein requirements should be at least 1.2–1.5 g/kg/day. Protein supports osteoid matrix synthesis and accelerates fracture healing. It also matters for preserving muscle mass.
• Micronutrients such as magnesium, phosphorus, and vitamin K also contribute to bone mineralization and are recommended as part of a balanced diet.

Lifestyle Changes

• Lifestyle changes support both fracture prevention and healing:
• Stopping smoking and alcohol use:
• Smoking suppresses osteoblast activity, disrupts estrogen metabolism, and delays fracture healing.
• Excessive alcohol reduces calcium absorption, disrupts vitamin D metabolism, and increases fall risk.

Improving home safety:

• Prevent slippery floors and secure rugs
• Install stair handrails
• Ensure beds and chairs are high enough
• Arrange lighting such as nightlights
• These changes are critical to preventing further fractures, particularly in older cancer patients and those with balance problems.

Special Situations Requiring Caution

Bone fractures in cancer patients are more complex and hazardous in certain clinical situations. Recognizing and appropriately managing these conditions is decisive for survival and quality of life.

Pathological Fractures

• Pathological fractures occur with less trauma than in normal bones (such as simply standing, sitting, or getting out of bed).
• Malignant tumor invasion, increased osteolytic activity, and microarchitectural damage reduce bone strength. This occurs particularly in solid tumors with bone metastases (such as breast, prostate, and lung cancer) and in multiple myeloma.
• The lesion surrounding the fracture should be assessed radiologically.
• Biopsy may be needed because a fracture can sometimes be the first sign of malignancy.
• Treatment should include not only fracture stabilization but also control of the primary tumor (chemotherapy, radiotherapy, targeted treatments).

Multiple Myeloma and Metastatic Bone Disease

• In multiple myeloma and cancers that metastasize to bone (breast, lung, prostate), tumor cells occupy the bone marrow microenvironment. This:
• Disrupts the RANKL/OPG balance and increases osteoclast activity.
• Causes widespread osteolytic lesions and bone fragility.
• Treatment: Bone-protective agents (zoledronic acid, denosumab) must be planned alongside antitumor treatment (such as bortezomib, lenalidomide, daratumumab).
• Lesions at risk of fracture may require prophylactic surgical stabilization (e.g., Mirels score ≥9).

Steroid Use

• Steroids are frequently used, particularly in hematologic malignancies and to reduce brain edema.
• However, prolonged (>3 months), high-dose systemic steroid use inhibits osteoblast function, increases osteoclastic resorption, reduces calcium absorption, and causes glucocorticoid-induced osteoporosis.
• High-risk patients should have a DEXA scan before treatment
• Calcium (1000–1200 mg/day) and vitamin D (800–1000 IU/day) supplements should be recommended
• Bisphosphonates or denosumab may be planned prophylactically.

Kidney Function

• Because bisphosphonates are renally excreted, they require caution or may be contraindicated in patients with glomerular filtration rate (GFR) <30 mL/min.
• Denosumab is not renally excreted and can therefore be used safely in patients with renal impairment. However, it requires close laboratory monitoring for hypocalcemia.
• Before Administration: Monitor serum creatinine, calcium, phosphorus, and 25(OH)D levels, and ensure hydration in patients scheduled to receive bisphosphonates.

Neurological Complications (Spinal Fractures and Spinal Cord Compression)

Spinal metastases or vertebral compression fractures may compress the spinal cord or spinal nerves, causing serious neurological symptoms:

• Sudden back or lower back pain
• Motor weakness, difficulty walking
• Sphincter dysfunction (urinary retention, incontinence)

Emergency Intervention Is Required:

• Magnetic Resonance Imaging (MRI) assesses spinal cord compression.
• High-dose steroids (such as dexamethasone) are given to reduce edema.
• Spinal compression should be relieved through neurosurgery and/or emergency radiotherapy.

Note: Delayed diagnosis increases the risk of irreversible paraplegia.