A. Risks for Fractures

1. Trauma
2. Osteoporosis [12,34]
3. Sex Hormone Deficiency
   1. Estrogen deficiency - menopause, pituitary disease, iatrogenic
   2. Testosterone deficiency including androgen deprivation therapy [1]
4. Neoplastic Disease
   1. Direct invasion of bone (breast, prostate, myeloma, others)
   2. Secretion of hormones which reduce bone mass (lymphomas, squamous carcinomas)
5. Elevated Homocysteine Levels [2,3,4]
6. Various hereditary bone diseases
7. Use of ß-adrenergic blockers associated with ~20% reduced risk for fractures [5]
8. Biochemical Markers
   1. Low levels of RANK ligand [6]
   2. Collegen type 1 gene polymorphisms
   3. Estrogen receptor alpha polymorphisms
   4. ß-crosslaps levels
9. ESR1 (estrogen receptor alpha) polymorphisms associated with fracture, not bone density [7]
10. Long term proton pump inhibitor (PPI) associated with 1.2-1.6X increased fracture risk [37]

B. Types of Fractures

1. Closed Skin (Simple)
2. Open (Compound)
3. Traumatic
4. Pathologic Fracture (Differential)
   1. Osteopenia / Osteoporosis - vertebral, hip, other long bones
   2. Metastatic Disease: Lung, breast, prostate, colon, multiple myeloma, ovarian
   3. Renal Osteodystrophy
   4. Primary Bone Tumors and Bone Cysts
   5. Paget's Disease
   6. Hyperparathyroidism: cortical tunneling, subperiosteal bone resorption
   7. Rickets: growth plate too wide
   8. Osteopetrosis: marble bone, very dense
   9. Scurvy: ubperiosteal hemorrhage
   10. Infection: Osteomyelitis
   11. Radiation Therapy [33]
5. Comminuted means >1 break
6. Incomplete
   1. Greenstick
   2. Plastic
   3. Torus (Buckle)
7. Avulsion [8]
   1. Bone lost due to trauma or disease
   2. Tissue engineered bone may be useful for avulsion
8. Union of Fracture
   1. Delayed
   2. Slowed
   3. Non-union
   4. Pseudoarthrosis
   5. Malunion

C. Stress Fracture

1. Small fractures through lines of stress
2. Usually through 1-2 trabeculae or through the cortex
3. Hemorrhage and edema lead to periosteal inflammation which causes pain
4. Bone scan and MRI may detect fractures
5. In some patients, a significant inflammatory effusion can develop

D. Hip Fracture [9]

1. Major cause of loss of independence in both female and male elderly population
   1. Associated with ~15% excess mortliaty in first year
   2. Functional disability in most survivors
   3. Up to 17% (1 in 6) of white women in USA sustain hip fracture after age 50
   4. Worldwide, >30% of all hip fractures occur in men, usually associated with osteoporosis [40]
   5. Screening for risk factors and preventive therapy is critically important
2. Types
   1. Femoral neck
   2. Intratrochanteric
   3. Subtrochanteric
3. Risk Factor Overview
   1. Osteoporosis is greatest risk factor
   2. Lowest quartile body weight is a 2X risk factor for hip fracture versus highest quartile [10]
   3. Stroke associated with 2-4X increased risk versus age-matched non-stroke controls [2]
   4. Increasing Age
   5. Postmenopausal women with undetectable serum estrogen levels
   6. Elevated homocysteine levels [2]
   7. Syndromes associated with loss of consciousness
   8. Excessive intake and elevated serum levels of vitamin A [11]
   9. Occult vitamin D deficiency (usually with high parathyroid hormone, PTH)
   10. Chronic renal failure and dialysis (secondary hyperparathyroidism) [13]
   11. Renal transplantation (glucocorticoids exacerbate bone loss) [13]
   12. Inflammatory Bowel Disease - fracture risk increased 40% (osteopenia associated) [14]
4. Hip Fracture Risk Prediction Rule for Postmenopausal Women [39]
   1. Age
   2. General health
   3. Weight
   4. Height
   5. Fracture after age 55 years
   6. Race/ethnicity
   7. Physical activity
   8. Current smoking
   9. Parent broke hip
   10. Glucocorticoid use
   11. Diabetes
   12. These 11 factors account for ~80% of all hip fractures
5. Prevention [9]
   1. Approved treatments for osteoporosis (bisphosphonates > hormone replacement)
   2. Risedronate reduces hip fracture risk 30% in osteoporotic women >70 years [35,36]
   3. Alendronate clearly reduces fracture risks [36]
   4. Statins probably do not reduce the risk of hip fracture [16,17]
   5. Calcium 1gm/day + Vitamin D 800IU/day (in patients with abnormally low levels)
   6. Calcium + Vitamin D did not reduce fractures in elderly with previous low-trauma fractures [32]
   7. Walking and leisure time activity (versus inactivity) [18]
   8. External hip protector can prevent fractures in frail adults >70 years [19]
   9. Current thiazide diuretic use associated with ~50% reduction in risk for hip fracture [20]
   10. Folate and mecobalamin (Vitamin B12) supplements associated with 75% reduction in risk of hip fracture in Japanese patients with stroke after 2 years [2]
6. Issues in Medical Management of Fractures
   1. Timing of surgery - within 24-48 hours in medically stable patients
   2. Prophylactic antibiotics - should be given 0-2 hours before and through 24 hours after surgery; cephazolin 1-2gm q8 hours or similar agent is recommended
   3. Thromboembolism prophylaxis - low dose standard heparin or low molecular weight heparin (or low dose warfarin) should be used in ALL patients
   4. Nutritional status should be assessed proactively optimized
   5. Many elderly patients are malnourished, particularly with regards to protein
   6. Urinary tract - indwelling catheters should be removed within 24 hours of surgery
   7. For patients requiring longer catheterization, use intermittant straight catheterization
   8. Delirium risk factors should be assessed and avoided
7. Complications of Hip Fracture
   1. Osteonecrosis of femoral head
   2. Thromboembolism (risk reduced with prophylaxis)
   3. In elderly persons, peri-fracture bone loss is observed
   4. Delirium
   5. Malnutrition - elderly persons with fractures should maintain high protein intake
   6. Good nutrition maintains normal levels of serum IGF-1 and reduces perifracture bone loss
8. Treatment
   1. Surgery usually required - preferred early in course in stable patients
   2. Plaster casting for extended period
   3. Hip replacement
   4. Rehabilitation with fairly early mobilization is recommended
   5. Assessment of falls is critical
   6. Aggressive treatment of osteoporosis
   7. External hip protectors in osteoporotic, elderly adults did not prevent hip fractures [22]
   8. Zoledronic acid (Zometa®), a bisphosphonate, 5mg IV given annually following a hip fracture, reduces risk of subsequent vertebral and nonvertebral fractures [38]
9. Total Hip Replacement (THR) [21]
   1. Consists of acetabular cup with ball and stem components replacing femoral head
   2. Both cemented and uncemented give >15 year 50% intact THR
   3. Large bore bearings have good range of motion, stability, and very low wear
   4. Minimally invasive surgery limits soft-tissue damage, facilitates hospital discharge
   5. Computer assisted surgery provides very accurate positioning of implants
   6. Increasingly popular operation in both young and older personsk
10. Bisphosphonate therapy (zoledronic acid) after hip fracture reduces future fractures [38]

E. Vertebral Fractures [23]

1. Most common complication of osteoporosis
2. 3-4 times more common in women than men
3. Most (~70%) found on plain radiography; remainder diagnosed in clinical practice
4. Symptoms and Signs
   1. Presenting with back pain, limitation of motion
   2. May also lead to kyphosis and/or height shrinkage
   3. Neurologic compromise
   4. Reduced lung function
   5. Protuberant abdomen (difficulty bending over)
5. Prevalence of Radiographic Vertebral Fractures
   1. Age 50-54: 5%
   2. Age 80-84: 50%
6. Initial Vertebral Fracture
   1. Increases risk of a new vertebral fracture within 1 year by 5X [24]
   2. Associated with increased risk for hip fracture
   3. Increased mortality risk
7. Laboratory Evaluations for Patients with Vertebral Fracture [23]
   1. Complete blood count
   2. Serum calcium
   3. Serum alkaline phosphatase
   4. Serum creatinine
   5. Urinary calcium excretion
   6. Bone mineral density scan (BMD) should be performed
8. Neoplasms in Young Persons with Vertebral Fractures (Table 1, Ref [25])
   1. Hodgkin's and Non-Hodgkin's Lymphoma
   2. Acute leukemia
   3. Neuroblastoma
   4. Rhabdomyosarcoma
   5. Primative Neuroectodermal Tumors
   6. Germ-cell Tumor
   7. Medulloblastoma
   8. Wilms' Tumor
   9. Primary Bone Tumors: Osteogenic and Ewing's Sarcoma
   10. Eosinophilic Granuloma
   11. Giant Cell Tumor
   12. Osteochondroma
   13. Osteoblastoma
   14. Osteoid Osteoma
   15. Benign: Hemangioma, Aneurysmal Bone Cyst
9. Further Evaluations as Clinically Indicated [23]
   1. Serum 25-hydroxyvitamin D - rule out vitamin D deficiency
   2. Parathyroid hormone (PTH) - rule out hyperparathyroidism
   3. Serum protein electrophoresis (SPEP) - rule out monoclonal gammopathy
   4. Bioavailable testosterone and gonadotropins in men
   5. Aminotransferase levels - rule out liver disease
   6. Thyroid stimulating hormone (TSH) - rule out hyperthyroidism
10. Treatment
    1. Symptomatic at present
    2. Pain control with acetaminophen (up to 2.4 gm/d)
    3. Celecoxib (Celebrex®) can be used chronically but must monitor renal function
    4. Breakthrough pain managed with tramadol (Ultram®) or codeine
    5. Calcitonin 200IU intranasal may be effective in acute pain
    6. Intercostal nerve blocks may improve chronic pain
    7. Vertebral fusion may improve pain
11. Vertebroplasty [26,27]
    1. Vertebroplasty is injection of cement to stabilize fractured vertebral body
    2. Rapidly stabilizes spine and improves pain
    3. Procedure is perfermed percutaneously and fairly rapidly
    4. Pain relief is prompt (within 24 hours) and durable
    5. Nearly 25% of patients can cease all analgesia within 24 hours
    6. In inpatients, vertebroplasty reduced hospital stay versus conservative by >30%
    7. At 6 weeks, no better than conservative treatment
    8. Kyphoplasty involves inflating balloon into fracture then cementing enlarged area
    9. Theoretically, kyphoplasty will restore height lost with vertebral fractures
12. Prevention
    1. Calcium and vitamin D intake should be optimized
    2. Calcium + Vitamin D did not reduce fractures in elderly with previous low-trauma fractures [32]
    3. Second generation bisphosphonates (such as alendronate) are very effective [28]
    4. Hormone replacement therapy (HRT) and SERMS also reduce fracture risk
    5. HRT also prevents non-vertebral fractures ~27% [29]
    6. Raloxifene (Evista®), a SERM, is generally preferred over HRT [30]

F. Stages of Healing of Fractures

1. Hematoma
2. Granulation Tissue
3. Cartilage Deposition: Osteoid formation (bone prior to mineralization)
4. Bone reformation and Remodelling
5. Time frame of healing
   1. Hand 1-3 weeks
   2. Tibia and Femur (Large bones) 2-4 months
6. Most bone fractures heal with histologically normal tissue in the presence of adequate stability (usually with internal or external fixation) and vascularity [31]

G. Complications of Fractures

1. Necrosis
2. Nonunion
3. Nonunion with Pseudoarthrosis
4. Malunion
5. Cholesterol (fat) emboli
6. Thromboembolism (lower extremity)
7. Pain

H. Other Complications

1. Pathologic fracture: fracture due to previously sick bone
   1. Osteo imperfecta
   2. Osteomyelitis (weakened area)
2. Myositis Ossificans
   1. Injury (trauma), usually with bleeding, to local tissue which is then gets ossified
   2. May shrink on its own.
   3. Also called heterotopic ossification
   4. Treatment: excision after maturation (may regrow if not mature)
3. Lower Extremity Fractures
   1. Increased incidence of deep vein thrombosis (DVT)
   2. Increased incidence of pneumonia in bedbound patients

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