34.1 Introduction

For many patients, the diagnosis of a vertebral compression fracture (VCF) is often the first indication of osteoporosis. It is also an opportunity to provide patients with appropriate treatment and education about the disease.

Osteoporosis, a systemic disorder of altered bone strength, continues to be an under-recognized condition, despite having a greater associated burden of disability (e.g., loss of work days, pain) than all sites of cancer, with the exception of lung cancer. Despite available screening tools, advances in pharmacologic therapy, and widespread education regarding exercise and adequate nutrient intake, the diagnosis and treatment rates of osteoporosis in the United States fall well below standards set by the National Osteoporosis Foundation (NOF) guidelines. ^{1 , 2}

The year following an initial fragility fracture (which is defined as any fracture resulting from a fall from standing height or less) holds the greatest risk for subsequent fractures. One-fifth to nearly one-half of patients experience another fracture within the year after the initial fragility fracture. ^{3 – 5} Unfortunately, only one-fourth of patients who sustain a fragility fracture (including a vertebral fracture) are formally diagnosed with osteoporosis within the year, despite the fact that sustaining a fragility fracture is a defining event of osteoporosis ^{6 – 8} and only one-fourth of patients who experience an osteoporotic fracture are on pharmacologic osteoporosis therapy at 1 year, putting them at higher risk for additional fractures. ^{9 , 10}

34.2 Etiology and Epidemiology

As osteoporosis is a bone disorder characterized by decreased bone strength, it increases the risk of fracture. Bone strength is composed primarily of two components: bone density and bone quality. Bone density is determined by peak bone mass and the rate of subsequent bone loss, and is expressed as grams of mineral per area or volume. Bone quality refers to architecture, turnover, damage accumulation (e.g., micro-fractures) and the degree of mineralization. ¹¹ Osteoporosis results from an imbalance between bone formation and bone loss, with formation being less than loss as well as diminished bone quality. When a failure-inducing force is applied to osteoporotic bone, which can even be normal force on a weakened bone, a fracture occurs. ¹¹

Osteoporosis occurs in both sexes, but is more often recognized and diagnosed in women following menopause (▶Fig. 34.1). ¹¹ Both men and women have an age-related decline in bone mineral density (BMD) in midlife due to increased bone resorption as compared to bone formation, though women experience a more rapid bone loss in the early years after menopause. ¹¹ Fractures in men typically occur about a decade later than in women. Peak bone mass is not completed until age 30, after linear bone growth has ceased. Therefore, bone mass attained early in life may be the most important determinant of skeletal health later in life. ^{11 , 12}

Peak bone mass may be affected by genetic and lifestyle factors including nutrition (lifetime calcium and vitamin D intake), physical activity, smoking, alcohol, eating disorders, autoimmune diseases, glucocorticoid medications, and endocrine disorders that affect sex steroids. ¹² Characteristics associated with low bone mass later in life include female sex, increased age, estrogen deficiency, white race, low weight and body mass index (BMI), and family history of prior fracture. ¹¹ The list of possible secondary causes is lengthy and includes endocrine and metabolic conditions, nutritional or collagen metabolism disorders, and drug side effects. Conditions that may contribute to low bone mass include genetic diseases, hypogonadal states, malabsorption disorders, celiac disease, Crohn disease and gastric bypass, multiple myeloma, malignancy, rheumatologic and autoimmune diseases, end-stage renal disease, and post-organ transplantation status. ¹³

34.3 Economic Burden

Osteoporosis and associated osteoporotic fractures have a profound effect on individual morbidity and mortality and are exceedingly common. The NOF estimates that 10.2 million Americans have osteoporosis and that an additional 43.4 million individuals have low bone mass.

There were an estimated 2 million fractures attributable to osteoporosis in 2005, with 27% of the fractures occurring at vertebral sites. ¹⁴ Not only are the fractures quite common, the economic burden and public health impact are immense. It is estimated that over 400,000 hospital admissions, 2.5 million medical office visits, and 180,000 nursing home admissions were related to osteoporotic fractures in 2004. ¹⁵ Hospital costs for a single inpatient admission related to vertebral fracture may total approximately $12,000. ¹⁶

Vertebral fractures are roughly twice as common as a hip fracture and are the most common type of osteoporotic fracture. Vertebral insufficiency fractures indicate a high risk for future fractures regardless of whether or not the bone density testing (T-score) meets the threshold for osteoporosis. ¹⁴

Significant costs related to fracture care are incurred by inpatient care, long-term care facilities, and outpatient care. ¹⁷ In the year following a fracture, medical and hospitalization costs were 1.6 to 6.2 higher than prefracture costs and 2.2 to 3.5 times higher than those for age-matched controls with costs totaling up to $71,000 for a hip fracture and up to $68,000 for a vertebral fracture. ¹⁸ Medicare pays for approximately 80% of these fragility fracture costs. ¹⁷ Given the recent prominent increase in the age of the population, the cost of care of osteoporosis is expected to rise to $25.3 billion by 2025. ¹⁷ In addition to the medical costs, indirect costs are also prominent, including the price of reduced productivity due to disability and reduced workforce participation, and patients are also at substantial risk of premature death. ¹⁵

Failure to detect clinical osteoporosis when it is present likely contributes to the current lack of awareness of the consequences of the disease by both clinicians and patients. This impacts the reimbursement strategies of payers, influences policy makers in the public health sector by underestimating the number of those at increased fracture risk, and affects the design of clinical trials of new agents to reduce fracture. ¹⁹

34.4 Presentation and Diagnosis

Screening at-risk populations for osteoporosis is essential. In the case of a patient presenting after vertebral augmentation, the diagnosis of osteoporosis is a foregone conclusion, provided the vertebral fracture was a fragility fracture. Many vertebral fractures, however, are silent and often go undiagnosed.

Based on guidelines from the World Health Organization (WHO) and the NOF, the diagnosis of osteoporosis may be made by meeting any one of these criteria: the presence of a fragility fracture in the absence of other metabolic bone disorders or high velocity trauma; a T-score of −2.5 or lower on DXA imaging, even in the absence of a prevalent fracture and in patients with osteopenia and an increased fracture risk, using Fracture Risk Assessment Algorithm (FRAX) country-specific thresholds. ^{13 , 14 , 19 , 20} (See “Fracture Risk Assessment Algorithm (FRAX below.)

Since approximately 30% of osteoporosis cases in postmenopausal women are believed to be due to a secondary cause, a thorough history, physical exam, and laboratory testing could be performed to identify secondary causes. ^{1 , 14 , 19} Laboratory testing may include:

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  Complete blood count (CBC).

  
  
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  Serum chemistries (calcium, phosphorus, renal, and liver function tests).

  
  
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  Thyroid-stimulating hormone (TSH).

  
  
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  25-Hydroxy vitamin D3 (25(OH)D.

  
  
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  Intact parathyroid hormone (PTH).

  
  
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  Serum/urine protein electrophoresis.

  
  
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  Serum/urine immunofixation electrophoresis.

  
  
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  Serum-free light chains.

  
  
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  Tissue transglutaminase antibodies and total IgA.

  
  
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  Urine calcium/creatinine ratio +/− 24-hour urine for calcium excretion (including urine sodium and creatinine to assess the adequacy of collection).

  
  
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  Bone turnover markers (BTMs) in select patients:

  
  
  
  
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    Bone resorption markers: Collagen cross-linked N-telopeptide (NTX), collagen type 1 c-telopeptide (CTX).

    
    
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    Anabolic markers: Procollagen 1 propeptide (P1NP), bone-specific alkaline phosphatase (BSAP).

In patients with clinical or biochemical evidence of malabsorption, celiac antibodies should be obtained. Serum and urine protein electrophoresis may be obtained if there is a suspicion for multiple myeloma (e.g., non-PTH-mediated hypercalcemia). ¹⁴ Also in select cases, urine-free cortisol, testosterone, follicle-stimulating hormone (FSH), and tryptase levels may be indicated. It should be noted that the 24-hour urine calcium collection must occur after the patient is vitamin D replete and has been on a reasonable calcium intake (1,000–1,200 mg/day) for at least 2 weeks.

34.5 Dual-Energy X-ray Absorptiometry

Dual-energy X-ray absorptiometry (DXA) imaging can provide valuable information in the diagnosis of osteopenia and osteoporosis and in the monitoring of BMD. In general, DXA imaging should be ordered for screening in all women age ≥ 65 years of age, men age ≥ 70, postmenopausal women and men age 50–69 based on risk factor profile, and postmenopausal women and men age ≥ 50 who have had an adult age fracture. ¹³

BMD is measured with DXA of the lumbar spine (on the anteroposterior view), femoral neck, and total hip. The distal one-third of the radius should be scanned in individuals with hyperparathyroidism, in those who do not have a valid spine or hip site, or in individuals whose weight exceeds the maximum limit of the table. ²⁰ Area BMD is expressed in g/cm² and as a relationship to two norms: the BMD of an age-, sex-, and ethnicity-matched reference population (Z-score) or a young-adult reference population of the same sex (T-score). The difference between the patient’s BMD and the mean BMD of the reference population, divided by the standard deviation (SD) of the reference population, is used to calculate Z- and T-scores. ¹³ In postmenopausal women and men age 50 and older, the WHO diagnostic T-score criteria are applied. In premenopausal women, men less than 50 years of age, and in children, the ethnic or race-adjusted Z-scores should be used. ²¹ In premenopausal women and men less than age 50, a Z-score ≤ −2.0 is BMD below the expected range for age and a Z-score > −2.0 is BMD within the expected range for age (see ▶Fig. 34.2).

The WHO criteria for the diagnosis of osteoporosis based on BMD (T-scores) using DXA measurement are as follows:

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  Normal: T-score ≥ −1.0 SD.

  
  
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  Low bone mass: −2.5 SD < T-score < −1.0 SD.

  
  
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  Osteoporosis: T-score ≤−2.5 SD.

  
  
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  Severe osteoporosis: T-score ≤−2.5 plus one or more fragility fractures. ²²

Along with traditional DXA imaging, other DXA-based tools have been developed to assist the clinician in the evaluation and prediction of risk of fracture for individual patients. These tools include vertebral fracture assessment (VFA), trabecular bone score (TBS), extended femur scans to detect incomplete atypical femoral fractures, vertebral radiographs, and FRAX.

34.6 Vertebral Fracture Assessment

Vertebral fracture assessment (VFA) is a measurement tool that uses lateral images obtained by DXA to identify asymptomatic vertebral fractures. VFA should be performed if the results may alter the decision to treat or not to treat, change the drug selected for treatment, or affect the follow-up of the patient. ²³ Three patterns of vertebral deformation have been described in VFA: wedge, biconcave, and crush. ²⁴ Up to 25% of patients over age 60 who are being evaluated for osteoporosis have been found to have vertebral fractures with only 11% of those patients reporting a history of vertebral fracture. ²⁵ Using VFA to identify individuals with asymptomatic vertebral fractures as part of a comprehensive risk assessment may aid in clinical decision-making. ^{23 , 26} Detection of vertebral fractures has traditionally relied on standard radiographs of the spine, which are associated with cost and radiation exposure and require a separate visit. Therefore, radiographs are usually not obtained in the standard evaluation of patients with osteoporosis. ²⁵ Using DXA technology, radiation exposure and cost can be lessened, and vertebral anatomic information is available to the physician at the patient’s clinic visit. ²⁵

34.7 Radiographs

In addition to VFA, vertebral imaging with AP, lateral, and in some cases oblique and spot views is indicated in all women age ≥ 70, all men age ≥ 80 if BMD is ≤ −1.0 at the spine, total hip, or femoral neck, in women age 65 to 69 and men age 70 to 79 if BMD T-score is ≤ −1.5 at the spine, total hip, or femoral neck. ^{13 , 23} Vertebral imaging is also indicated in postmenopausal women and men age ≥ 50 with the following specific risk factors: low-trauma fracture during adulthood (age 50 and older), historical height loss (difference between the current height and peak height at age 20) of 1.5 inches (4 cm) or more, prospective height loss (difference between the current height and a previously documented height measurement) of 0.8 inches (2 cm) or more, or recent or ongoing long-term glucocorticoid treatment. ^{13 , 23}

34.8 Trabecular Bone Score

Trabecular bone score (TBS) is an analytical tool that uses measurements on the lumbar spine DXA to capture information related to trabecular microarchitecture. The TBS decreases with age and reflects qualitative aspects of skeletal structure that complements the quantitative measurement of BMD. ²⁷ Low TBS is consistently associated with an increase in fractures and is partly independent of both clinical risk factors and BMD at the lumbar spine and proximal femur. ²⁸ Therefore, this technique may aid in clinical decision-making regarding the need for pharmacologic therapy or the type of medication used. More studies are needed to determine the optimal clinical use of TBS.

Extended femur scanning by DXA is a screening tool that is used to detect incomplete atypical femur fractures in patients on antiresorptive therapy. Though individuals with atypical femur fractures may present with prodromal groin or thigh pain, others are asymptomatic. ^{29 , 30} This tool may be considered in individuals who have previously sustained an atypical femoral fracture, bisphosphonate users who report pain in the hips, groin, or upper legs, and in individuals who have taken antiresorptive therapy for more than five years or have other risk factors for developing an atypical femoral fracture. ²⁹

34.9 Fracture Risk Assessment Algorithm (FRAX)

FRAX is a risk assessment tool that can be used to estimate the 10-year fracture risk with or without femoral neck BMD. FRAX is a country- and ethnicity-specific fracture risk assessment that combines BMD at the femoral neck (or total hip) with a group of well-validated and weighted clinical risk factors for fracture that are largely independent of BMD. ³¹ Age and mortality are taken into account, which are unique benefits of this algorithm. Other factors in the algorithm include gender, height, weight, BMI, personal fracture history, parental history of hip fracture, glucocorticoid use, rheumatoid arthritis, and the current use of tobacco and excessive alcohol intake. Treatment is indicated or suggested when the 10-year probability of a major osteoporotic fracture (spine, forearm, hip, or shoulder) is ≥ 20% or the 10-year probability of hip fracture is ≥ 3%. FRAX does have limitations and is most appropriate in patients with low femoral neck BMD. Using FRAX in patients with low BMD at the lumbar spine but a relatively normal BMD at the femoral neck will underestimate fracture risk in these individuals. Furthermore, it may also underestimate fracture risk in patients with recent fractures, multiple osteoporosis-related fractures, and those at increased risk for falling. ¹³ FRAX (▶Fig. 34.3) can be accessed at: https://www.sheffield.ac.uk/FRAX/index.aspx.

34.10 Treatment

Treatment of osteoporosis is indicated in any patient with a low velocity fracture or a hip or vertebral fracture (regardless of BMD). ^{13 , 20 , 21 , 32} Pharmacological osteoporosis therapy should be considered in any patient with a T-score of ≤ −2.5 at the femoral neck, total hip, lumbar spine, or distal one-third of the radius or one with a T-score between −1.0 and −2.5 (osteopenia) and increased fracture risk by FRAX (10-year hip fracture risk of ≥ 3% or a 10-year major osteoporosis-related fracture probability ≥ 20%). ^{13 , 20} Pharmacological therapy is also indicated in patients who are at moderate-to-high risk of fracture on glucocorticoid therapy. ³³

Related posts:

4 Physical Examination Findings in Patients with Vertebral Compression Fractures 13 Radiation Exposure and Protection: A Conversation Beyond the Inverse Square Law, Thermoluminescent Dosimeters, and Lead Aprons 16 Cost-Effectiveness of Vertebral Augmentation 14 Appropriateness Criteria for Vertebral Augmentation 25 Postural Fatigue Syndrome 29 Treatment of Neoplastic Vertebral Compression Fractures

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