Orthopaedic surgeons need to have a fundamental understanding of the metabolic bone diseases discussed in this chapter because these diseases compromise bone strength and increase fracture risk, including fragility fractures. A considerable number of patients treated by orthopaedic surgeons, particularly in the population older than 50 years, are at risk for a metabolic bone disease, including those patients who seek elective orthopaedic care, such as joint replacement and spine surgery. Compromised bone strength can contribute to the failure of surgical fixation and stability of the implant-bone interface. Knowledge of the diagnostic modalities and pathophysiology will help orthopaedic surgeons take an active role in the diagnosis and treatment of these diseases and the avoidance of surgical complications.

Maintenance of serum calcium concentration is a homeostatic priority because cell membrane signaling and neuromuscular signal transmission are highly sensitive to serum and extracellular calcium concentrations. Cellular responses to several hormones, excitation-contraction coupling in cardiac muscle, and skeletal muscle contraction depend upon calcium concentrations within a narrow physiologic range. To accomplish this homeostatic priority, three organ systems, gastrointestinal, renal, and skeletal, the parathyroids, parathyroid hormone (PTH), and vitamin D (1,25(OH)₂D), interact in an elaborate series of physiologic mechanisms to regulate serum calcium concentration.¹ Vitamin D and PTH maintain the concentrations of ionized calcium and phosphate at levels consistent with normal neuromuscular function and within safe range of the solubility product of CaHPO₄.

Among the organs supporting serum calcium, bone is unique in that its role as a calcium donor can compromise its structure and lead to fracture. Among the physiologic roles of bone, its role as a calcium donor can take precedence over its structural roles leading to the perspective that the primary function of bone is as the calcium reservoir for serum calcium concentration. Because of the priority to maintain serum calcium concentration, needs for serum calcium or disorders of the integrated physiologic mechanisms to support serum calcium can lead to loss of calcium from bone characterized as metabolic bone diseases, loss of bone mass, structural failure, and fracture. A type of fracture seen with decreased bone density is the fragility fracture defined as a fracture due to a fall from a standing height or with minimal trauma.

Fractures, especially hip fractures, not only cause mortality and morbidity, but also significantly increase health care costs. In 2005, $17 billion was spent for more than two million fractures in the United States, and the cost is expected to increase.³ As a fracture is a multifactorial event, it is imperative to assess both skeletal integrity—bone quantity and quality—and the risk of falls when estimating fracture risk. All postmenopausal women, and men aged 50 years or older, should be screened for the risk of osteoporosis. Important clinical risk factors include age ≥65 years, early menopause (age ≤45 years), prior history of fracture, history of parents having a fracture, and a history of malnutrition or eating disorder during adolescence and puberty that potentially prevents the attainment of peak bone mass. Lifestyle factors such as smoking and excessive alcohol intake can also impair bone strength. Attention has been called to the role of falls in fracture risk⁴ (Figure 1). Many medical conditions and medications can contribute to falls particularly those resulting in visual deficits, such as glaucoma and cataracts, dehydration, postural hypotension, or loss of balance (Table 1).

High-risk patients for osteoporosis and fracture (eg, women ≥65 years, men ≥70 years, or younger patients with significant risk factors) should be tested for low bone density. The most common method of assessment is dual-energy x-ray absorptiometry (DEXA) in which soft tissue is extracted from the density analysis. Bone mineral density (BMD) is expressed in g/cm² and is a planar rather than a volumetric measurement. BMD measured at any skeletal site is a strong predictor of hip or vertebral fracture. The Z-score compares density to an age- and sex-matched cohort; the T-score compares density to a reference group at age 20 years. The current diagnosis of low bone density and decision for treatment are often based on the T-score. Based on World Health Organization criteria, a T-score of -1.0 or above is considered normal, between -1.0 and -2.5 as osteopenia, preferably termed low bone mass, and -2.5 or below is categorized as “osteoporosis.” Low BMD in the range of osteopenia or osteoporosis does not indicate a specific disease entity because DEXA does not discriminate between osteoporotic and osteomalacic bone structure. Metabolic bone histopathology can be highly characteristic and often diagnostic (Figure 2).

There are a number of helpful tools to assess fracture risk. Among them, the Fracture Risk Assessment Tool, or FRAX, is the most commonly used in clinical practice because it is well validated in large cohort studies and freely available (www.sheffield.ac.uk/FRAX/). FRAX predicts 10-year risks of hip fracture and major osteoporotic fractures (eg, spine, hip, proximal humerus, and distal forearm fracture) using easily accessible clinical risk factors for osteoporosis together with femoral neck bone mineral density in the FRAX calculation.

Measuring BMD using DEXA has inherent limitations because it measures areal BMD (aBMD, g/cm²) not volumetric BMD (vBMD, g/cm³). Patients with a smaller bone size, such as women or short individuals, can have lower aBMD despite having the same vBMD compared with age-matched counterparts. Additionally, artifacts from vertebral fractures, arthritic and degenerative changes (eg, sclerosis, osteophytes, osteochondrosis, etc), scoliosis, vascular calcification, laminectomy, and poor positioning can mislead clinicians with spuriously high or low results.

Importantly, DEXA does not assess bone quality, such as geometry, microarchitecture, trabecular connectivity, or bone turnover, which are critical determinants of bone strength. For that reason, large cohort studies have shown that skeletal health
assessment based on BMD alone underestimates the risk of fracture. The Manitoba Bone Density Program cohort showed that more than 60% of fractures in postmenopausal females occurred with normal BMD or low bone mass.⁵ Importantly, patients with type 2 diabetes have significantly high risks of fracture despite having normal or even high BMD.⁶

Osteoporosis is the most common cause of low bone density and is associated with low energy or, fragility, fractures. In the United States alone, 40 million adults suffer from osteoporosis or low bone density.¹³ Osteoporosis is characterized by low bone volume, endosteal resorption, cortical thinning and increased porosity, and trabecular thinning and loss of connectivity (Figure 3). Deterioration of bone microarchitecture significantly reduces bone strength and increases the risk of fracture. Radiographically, trabecular resorption is characteristic and endosteal resorption is seen as widening of the medullary canal (Figure 4).

Once osteoporosis is diagnosed, possible secondary causes should be sought and treated. Vitamin D deficiency (discussed below) is very common and can be diagnosed by measuring the storage form of vitamin D, (25(OH)D). Other conditions can result in low bone density and mimic osteoporosis including prominently the endocrine disorders, hyperparathyroidism, hypercortisolism, hyperthyroidism, diabetes, and hypogonadism. A variety of other conditions including premature menopause, anorexia nervosa, athletic amenorrhea, immobilization, and alcohol abuse can also result in osteoporosis. Other, more rare conditions that include osteoporosis are discussed in Chapter 25. Medications can also contribute to osteoporosis (Table 3). Important conditions associated with low bone mass are hormonal therapies, organ transplantation, and immunosuppression.