Residency · Residency · Orthopedic Surgery

Osteoporosis and Metabolic Bone Disease for the Orthopedic Surgeon

Introduction

Osteoporosis is the most common metabolic bone disease, affecting an estimated 10 million Americans with an additional 44 million having low bone density. Fragility fractures are the clinical consequence, causing significant morbidity, mortality, and healthcare costs. Despite being the physicians most likely to treat these fractures, orthopedic surgeons have historically underrecognized and undertreated the underlying metabolic disease. Closing this treatment gap is an essential responsibility.

Bone Biology Fundamentals

Bone remodeling is a continuous process mediated by the basic multicellular unit (BMU), which represents the coupled activity of osteoclasts (resorption) and osteoblasts (formation). The RANK/RANKL/OPG axis is the central regulatory pathway: RANKL, produced by osteoblasts and osteocytes, binds to RANK on osteoclast precursors to stimulate their differentiation and activation, while osteoprotegerin (OPG) acts as a decoy receptor that blocks RANKL and thereby inhibits osteoclast activity. Osteocytes serve as the master regulators of bone metabolism by producing sclerostin, which inhibits the Wnt signaling pathway and suppresses bone formation. Peak bone mass is achieved by age 25-30, after which bone mass gradually declines. Estrogen is a potent inhibitor of bone resorption, and its withdrawal at menopause accelerates bone loss dramatically.

Osteoporosis: Diagnosis and Classification

Definition

The WHO definition of osteoporosis is a bone mineral density (BMD) T-score of -2.5 or lower at the lumbar spine, femoral neck, or total hip on DEXA scan. Osteopenia is defined as a T-score between -1.0 and -2.5. Clinical osteoporosis can also be diagnosed when a fragility fracture occurs regardless of BMD.

DEXA Scan (Dual-Energy X-ray Absorptiometry)

DEXA is the gold standard for measuring BMD and reports values as a T-score (compared to a young adult reference population) and a Z-score (compared to an age-matched reference). A Z-score below -2.0 in a premenopausal woman or man under 50 suggests secondary osteoporosis warranting further evaluation. Screening is recommended for all women over 65, men over 70, and younger patients with risk factors.

FRAX Tool

The Fracture Risk Assessment Tool (FRAX) estimates 10-year probability of major osteoporotic fracture and hip fracture. It incorporates BMD, age, sex, BMI, prior fracture, family history, smoking, alcohol use, glucocorticoid use, rheumatoid arthritis, and secondary osteoporosis. Treatment is recommended if 10-year hip fracture risk exceeds 3% or major osteoporotic fracture risk exceeds 20%.

Secondary Causes of Osteoporosis

Secondary causes must be excluded, especially in premenopausal women, men under 50, and patients with Z-scores below -2.0. Endocrine causes include hyperparathyroidism, hyperthyroidism, Cushing syndrome, hypogonadism, and type 1 diabetes. Nutritional causes include vitamin D deficiency, calcium deficiency, malabsorption (celiac disease), and eating disorders. Medications are a major contributor, with glucocorticoids being the most common drug-induced cause, along with aromatase inhibitors, androgen deprivation therapy, anticonvulsants, and proton pump inhibitors. Hematologic conditions such as multiple myeloma and mastocytosis should be considered. Other causes include chronic kidney disease, chronic liver disease, rheumatoid arthritis, and immobilization.

Basic Laboratory Workup

The basic laboratory workup includes a comprehensive metabolic panel (calcium, phosphorus, albumin, creatinine), 25-hydroxyvitamin D level, complete blood count, and TSH. Additional studies to consider based on clinical suspicion include PTH, 24-hour urine calcium, serum protein electrophoresis, testosterone in men, and celiac panel.

Fragility Fractures

Epidemiology

Hip fractures occur in approximately 300,000 patients per year in the United States and carry a one-year mortality of 20-30% in the elderly. Vertebral compression fractures are the most common osteoporotic fracture, though many are clinically silent. Distal radius fractures are often the first fragility fracture and should be regarded as a sentinel event indicating underlying osteoporosis. Proximal humerus fractures are also common in elderly women. A prior fragility fracture doubles the risk of a subsequent fracture.

The Orthopedic Surgeon's Role

The orthopedic surgeon is often the first and only physician to evaluate a patient after a fragility fracture. Initiating a workup and treatment or ensuring referral for metabolic bone evaluation is critical. Fracture Liaison Services (FLS) are coordinator-based programs that identify fracture patients, initiate workup, and ensure treatment, reducing secondary fracture rates by 30-50%.

Pharmacologic Treatment

Antiresorptive Agents

Bisphosphonates

Bisphosphonates are the first-line treatment for most patients. They bind to hydroxyapatite and inhibit osteoclast-mediated bone resorption. Alendronate (Fosamax) is administered orally with weekly dosing. Risedronate (Actonel) is available orally with weekly or monthly dosing. Zoledronic acid (Reclast) is given intravenously with annual dosing and is preferred for compliance and after hip fracture. Bisphosphonates reduce hip fracture risk by 40-50% and vertebral fracture risk by 50-70%. A drug holiday after 3-5 years of oral therapy or 3 years of IV therapy may be considered for moderate-risk patients. Adverse effects include GI intolerance with oral formulations, atypical femoral fractures (rare, associated with prolonged use), and osteonecrosis of the jaw (rare, more common with oncologic doses).

Denosumab (Prolia)

Denosumab is a monoclonal antibody against RANKL that inhibits osteoclast formation and activity. It is administered as a subcutaneous injection every 6 months and reduces hip and vertebral fracture risk comparably to bisphosphonates. Unlike bisphosphonates, denosumab does not accumulate in bone and its effects are reversible upon discontinuation. Rebound vertebral fractures can occur if denosumab is discontinued without transition to a bisphosphonate. It is preferred in patients with renal insufficiency since it is not cleared by the kidneys.

Anabolic Agents

Teriparatide (Forteo)

Teriparatide is recombinant PTH (1-34) that stimulates osteoblast activity and new bone formation. It is given as a daily subcutaneous injection for up to 2 years and increases BMD more dramatically than antiresorptives, particularly at the spine. It is indicated for severe osteoporosis, patients who fracture on antiresorptive therapy, or glucocorticoid-induced osteoporosis. It must be followed by an antiresorptive agent to maintain gains.

Romosozumab (Evenity)

Romosozumab is a monoclonal antibody against sclerostin with dual action that increases formation and decreases resorption. It is administered as a monthly subcutaneous injection for 12 months and produces the most rapid and significant BMD increase of any available agent. It must be followed by antiresorptive therapy to maintain gains. A cardiovascular risk warning contraindicates its use in patients with recent MI or stroke.

Surgical Considerations in Osteoporotic Bone

Implant fixation is compromised in osteoporotic bone because screw purchase and pullout strength are reduced. Strategies to improve fixation include locking plates and screws, which provide angular stability and reduce reliance on screw-bone purchase; cement augmentation with PMMA injection through cannulated screws to improve pullout strength in the spine and proximal femur; blade plates and helical blades, which provide better fixation in cancellous bone than lag screws in some biomechanical studies; and longer constructs that span a greater length of bone to distribute forces. Arthroplasty may be preferable to internal fixation for certain fracture patterns in osteoporotic bone, such as femoral neck fractures and comminuted proximal humerus fractures. Vertebral augmentation (kyphoplasty, vertebroplasty) is indicated for painful compression fractures refractory to conservative management, restoring vertebral height and providing immediate pain relief.

Vitamin D and Calcium

The target serum 25-hydroxyvitamin D level is 30-50 ng/mL, achieved through supplementation with vitamin D3 (cholecalciferol) at 1,000-2,000 IU daily. Total calcium intake (diet plus supplement) should be 1,000-1,200 mg daily, with dietary calcium preferred over supplements when possible. Vitamin D and calcium are adjunctive and not standalone treatments for osteoporosis.

Key Clinical Pearls

Every fragility fracture is an opportunity to diagnose and treat osteoporosis; the orthopedic surgeon should initiate a metabolic bone workup or ensure referral, as a prior fracture doubles the risk of a subsequent fracture. Bisphosphonates remain first-line therapy for most patients, and zoledronic acid after hip fracture reduces mortality and subsequent fracture risk. Denosumab must not be discontinued without transition to a bisphosphonate due to the risk of rebound vertebral fractures. Anabolic agents (teriparatide, romosozumab) are indicated for severe osteoporosis and produce the most dramatic increases in BMD, but they must be followed by antiresorptive maintenance therapy.

References

1. Black DM, Rosen CJ. Postmenopausal osteoporosis. N Engl J Med. 2016;374(3):254-262.
2. Lyles KW, Colon-Emeric CS, Magaziner JS, et al. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med. 2007;357(18):1799-1809.
3. Saag KG, Petersen J, Brandi ML, et al. Romosozumab or alendronate for fracture prevention in women with osteoporosis. N Engl J Med. 2017;377(15):1417-1427.
4. Camacho PM, Petak SM, Binkley N, et al. American Association of Clinical Endocrinologists/American College of Endocrinology Clinical Practice Guidelines for the Diagnosis and Treatment of Postmenopausal Osteoporosis. Endocr Pract. 2020;26(Suppl 1):1-46.

Read this lecture as Markdown