Two mechanisms of action:
• Nitrogen containing bisphosphonates inhibit farnesyl pyrophosphate synthase (pamidronate, alendronate, risedronate, zoledronate, ibandronate).
• Non-nitrogen containing bisphosphonates disrupt the ATP metabolic pathway by generating synthetic ATP analogue leading to osteoclast apoptosis (etidronate, cloduronate, tiludronate).
iv. Adverse events:
• Gastrointestinal upset, esophagitis, esophageal ulcers. Contraindicated in patients who are unable to swallow or sit upright for 30 minutes following administration.
• Osteonecrosis of the jaw—rare, more common in patients with dental problems.
• Atypical femur fractures—subtrochanteric/proximal femoral shaft; associated with minimal or no trauma; radiographic features include transverse or short oblique, minimal comminution, medial spike, lateral cortical thickening. Risk is increased with prolonged use over 3 years.
b. Denosumab:
i. Monoclonal antibody to RANKL.
ii. Given every 6 months.
iii. Reduces risk of vertebral fractures by 68%, hip fractures by 40%, and nonvertebral fractures by 20%.
iv. Can be associated with atypical femur fractures, osteonecrosis of the jaw, and rebound increased bone turnover.
v. Indicated in patients with contraindication to bisphosphonate use.
c. Hormone replacement therapy:
i. Effective in reducing risk of all fractures.
ii. Not used commonly due to increased risk of cardiovascular disease, venous thrombosis, and breast cancer with prolonged use.
d. Raloxifene:
i. Selective estrogen receptor modulator (SERM).
ii. Estrogen agonist at bone and antagonist in other tissues (no increased risk of malignancy).
iii. Decreases risk of vertebral fractures only.
iv. Not commonly used.
e. Tibolone:
i. Partial agonist at estrogen, progesterone, and testosterone receptors.
ii. Reduces risk of vertebral fractures by 45% and nonvertebral by 26%.
2. Anabolic medications—increase bone turnover, result in net positive bone deposition.
a. Parathyroid hormone 1–34 and 1–84:
i. Partial fragment (1–34), teriparatide, commonly used in cases of severe osteoporosis and failure of treatment.
ii. Increased risk of osteosarcoma in animal models has not been reported in humans.
iii. Nonetheless, contraindicated in patients with conditions of increased bone turnover (Paget’s disease, open physes, unexplained elevation in alkaline phosphatase, previous external beam or implant radiation therapy).
3. Initiation of pharmacotherapy following fracture:
a. Animal studies show a delay in callus maturation following administration of bisphosphonates.
b. No clinical evidence to suggest that bisphosphonates retard bone healing when administered in the perioperative period for the proximal femur and distal radius.
4. Bisphosphonates should be stopped following treatment of atypical femur fractures.
VIII. Prevention
A. Decreasing fall risk—use of proper ambulatory aids, correction of poor visual acuity (cataract surgery), proper illumination of rooms, removal of obstacles to ambulation (remove clutter), rubber soled shoes to improve grip, skid-proof backing on rugs and carpets, use of a bath mat, install bathroom bars, readily accessible flashlight in the bedroom.
B. Dietary supplementation of calcium and vitamin D.
C. Fragility fractures
1. Important to recognize that BMD is one data point used to assess risk of fracture.
2. Original studies correlating BMD with risk of fracture calculated relative risk.
3. The WHO Fracture Risk Assessment Tool (FRAX) is a 12 question survey assessing key risk factors that is used to predict the chance of one sustaining an osteoporosis-related fracture in the next 10 years.
4. Fragility fracture risk factors are listed in ▶Table 10.1.
5. Following a fragility fracture (low-energy spine fracture, hip fracture, distal radius fracture, proximal humerus fracture, pelvic ring injury, sacral insufficiency fracture) the following labs should be ordered:
a. Serum calcium.
b. Parathyroid hormone.
c. Thyroid-stimulating hormone, free T4.
d. 25-hydroxycholecalciferol (vitamin D).
Table 10.1 Risk factors for fragility fracture
| • Age more than 65 years | • Excess alcohol consumption (over 3 units/day) |
| • First-degree relative with fractured hip | • History of falls |
| • Current tobacco use | • Glucocorticoid use |
| • Menopause prior to age 45 years | • Hyperthyroidism |
| • Lifelong low calcium intake | • Chronic lung disease |
| • Poor vision despite correction | • Endometriosis |
| • Minimal weight-bearing exercise | • Malignancy |
| • History of fragility fracture | • Chronic hepatic or renal disease |
| • Self-report health as “fair” or “poor” | • Hyperparathyroidism |
| • Weight less than 127 pounds | • Vitamin D deficiency |
| • Amenorrhea | • Cushing’s disease |
6. Consider a consultation to a dedicated metabolic bone clinic for ongoing management of bone health following discharge.
7. Order a physical therapy consultation for home safety evaluation to minimize the risk of falls.
Summary
The incidence of osteoporosis-related fragility fractures will most likely increase in the coming years. Focus has turned to prevention with use of calcium and vitamin D supplements and routine screening with dual-energy X-ray absorptiometry (DEXA) scans. Pharmacotherapy is indicated for patients with a T-score < −2.5, history of fragility fracture, or T-score in the osteopenic range (−1.0 to −2.5) coupled with a high risk of fracture according to the FRAX calculator. Several classes of medications are available for treatment. Bisphosphonates are considered first-line pharmacotherapy and have been shown to reduce the rate of hip and vertebral fractures. A coordinated approach involving the orthopaedic surgeon and primary care physician is necessary to initiate osteoporosis treatment and conduct appropriate follow-up.
Suggested Readings
Dell R, Greene D, Schelkun SR, Williams K. Osteoporosis disease management: the role of the orthopaedic surgeon. J Bone Joint Surg Am 2008;90(Suppl 4):188–194
Kates SL, Ackert-Bicknell CL. How do bisphosphonates affect fracture healing? Injury 2016;47(Suppl 1):S65–S68
Lagari V, Gavcovich T, Levis S. The Good and the Bad About the 2017 American College of Physicians Osteoporosis Guidelines. Clin Ther 2017 (November)
Miki RA, Oetgen ME, Kirk J, Insogna KL, Lindskog DM. Orthopaedic management improves the rate of early osteoporosis treatment after hip fracture. A randomized clinical trial. J Bone Joint Surg Am 2008;90(11):2346–2353
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