Osteoporotic Fragility Fractures


Demographics of Osteoporotic Fragility Fractures

Fragility fracture refers to those fractures that result from a fall from standing height or less and frequently occur in the hip, wrist, and spine. Osteoporosis is characterized by a combination of both a decrease in bone density and microarchitectural defects in bone. Fractures secondary to osteoporosis are, by strict definition, pathologic fractures. They occur in bones whose structural integrity and strength have been diminished by an underlying disease process. Osteoporotic fragility fractures have become a major health and economic concern in the United States that has reached epidemic proportions. Osteoporotic fragility fractures occur more frequently than heart attacks, strokes, and breast cancer combined. Strategies are continually being developed and refined both to prevent these fractures and to manage them when they occur.

The impact of osteoporotic fragility fractures in the United States will likely be felt more in the decades to come than ever before. After World War II and in the ensuing 18 years, the United States saw a dramatic increase in childbirth rates. In 2011 the first of these “baby boomers” turned 65 years of age; at that time approximately 13% of the US population was age 65 or older. In contrast, as more of the baby-boomer population reaches this milestone, it is estimated that by 2030 roughly 18% of the US population will be age 65 or older. During the period from 2011 to 2026, 78 million baby boomers will reach 65 years of age in the United States alone. During the 20-year period from 2010 to 2030, it is expected that the United States will see a rise in the elderly population significantly higher than that of the prior 20 years or of the following 20 years ( Fig. 22.1 ). The health concerns associated with an aging population, including fragility fractures, are not isolated to the United States. Osteoporotic fragility fractures are or will become a major health issue in all regions. In particular, nearly half of the world's hip fractures will occur in Asia by 2050, as that region is expected to see a dramatic increase in its total number of hip fractures. The aging of the population, along with the economic burden of providing healthcare that goes with it, will make prevention and management of osteoporotic fragility fractures an important health issue for many years to come.

Fig. 22.1, The average annual growth rate, in percentages, of the elderly population in the United States.

Concurrently, with the aging of the baby boomers, life expectancy in the United States is at an all-time high. In 1980 the life expectancy of a female living in the United States was 77.4 years of age. In 2015 that number had risen to 81.2. Furthermore, life expectancy increases as an individual ages. Therefore for a woman in the United States who has reached 65 years, life expectancy increases to 85.3 years.

Along with the increasing age of the population, one can find an increase in the activity level and health expectations of seniors in the United States. Advancing age is no longer synonymous with physical and functional decline. The health benefits of physical activity late in life are well described. Aging seniors expect to be active after retirement. Many delay retirement or take on new employment after departure from their lifelong careers. Recreational options for seniors today often include nearly everything that was possible at a younger age. These increased expectations of overall health and quality of life continue for many after a fragility fracture, with expectations to return to a level of functioning equal to that before their fracture. The reality of the situation currently, however, does not always live up to these expectations ( Fig. 22.2 ). With hip fractures many patients do not regain their preoperative physical function and are at increased risk of sustaining an additional osteoporotic fracture, and approximately 20% of seniors who sustain a hip fracture die within 1 year. In addition to the physical morbidity associated with hip fractures in the elderly, psychosocial consequences and loss of independence are common issues.

Fig. 22.2, Morbidity and mortality as a percentage of patients 1 year after sustaining a hip fracture.

Trends of Fragility Fractures

Recent evidence has suggested there may be a decreasing incidence of hip fracture and subsequent mortality over the past 10 years. The reasons for this are not entirely clear but are likely to be multifactorial. Bisphosphonates have been shown to reduce the risk of hip fracture, but it is unlikely that the reduction in hip fracture incidence is entirely due to bisphosphonate use alone. Dietary and lifestyle changes, such as fall prevention, smoking cessation, healthy diet and exercise, and calcium and vitamin D supplementation, all contribute to better bone health and probably play some role in this decreased incidence. Temporal and geographic variations have been shown to affect rates of hip fracture as well.

Despite the recent reports showing a decreased incidence of hip fractures, it is unclear if this reduced incidence will continue with time. Regardless, the population in the United States and much of the world continues to age. As it does, it is projected that the number of osteoporotic fragility fractures will markedly increase over the next 30 to 40 years.

Although the use of bisphosphonates has contributed largely to a decreased incidence of hip fractures, it has also resulted in the emergence of atypical patterns related to their use. A characteristic fracture pattern, first reported on in 2005, has been observed and linked to the chronic use of this class of medications. By 2009 the American Society for Bone and Mineral Research (ASBMR) created a task force to study this issue and their report was published in 2010 delineating criteria for diagnosis of atypical femoral fractures. This distinct fracture type has been described by the following: a transverse or short oblique fracture line, focal callus reaction, medial spike, and a lack of comminution. The prevalence of atypical fracture is not truly known at this time. It is suspected to occur in less than 1% of patients with chronic bisphosphonate use. Before 2010 widespread publicity about this problem had caused many patients and physicians to become reluctant to employ bisphosphonates as an antiresorptive therapy, and had led some experts to recommend a bisphosphonate drug holiday in select patients with a history of chronic bisphosphonate use. More recent studies have shown that these atypical fractures are rare in patients taking bisphosphonates for up to 5 years and should not be considered a reason to defer therapy.

Results of Fragility Fractures

Most of the literature reporting results after fragility fracture has looked at the effect of hip fracture on morbidity, mortality, and functional outcome in older individuals. The lifestyle and quality of life of a patient after hip fracture is drastically altered. Postfracture independence is often reduced. Patients require increased levels of care and attention secondary to loss of mobility and ability to perform independent activities of daily living (ADLs). Often, the extent of these functional losses dictates whether or not discharge to a short-term rehabilitation facility or skilled nursing facility is necessary.

Mobility and ambulatory status after surgical stabilization of a hip fracture have significant importance for a patient's functional recovery. Ability to ambulate is fundamental to a patient being able to perform ADLs. In a prospective study of 336 patients who were prefracture community ambulators, only 41% regained their preinjury ambulatory status after surgery, and the remaining 59% of patients all lost varying degrees of their preinjury ambulatory functional status. Some reports state that up to 22% of patients become nonambulators 1 year after suffering a hip fracture. Several risk factors have been identified as independent predictors of patients regaining their preinjury ambulatory status at 1-year follow-up, including patient age, American Society of Anesthesiologists (ASA) physical status classification level, type of fracture, timing of surgery, and preoperative ambulatory status. Patients 85 years or older, those with an ASA score of III or IV, those sustaining a femoral neck fracture, and patients with a delay in surgical treatment are less likely to obtain their prefracture ambulatory capacity at 1-year follow-up than patients younger than 85 years old, those with an ASA level of I or II and an intertrochanteric fracture pattern, and those receiving prompt surgical treatment. In addition, female gender, cognitive limitations (including a history of dementia and postoperative delirium), and a readmission to the hospital negatively affect a patient regaining his or her prefracture ambulatory status. A history of cerebrovascular accident with associated physical or cognitive limitations has also been shown to limit a patient's ability to regain ambulatory function after a hip fracture. Other factors, such as the surgical implant used and the type of anesthesia administered, have not been shown to influence the recovery of ambulatory function in patients 1 year after surgical treatment of a hip fracture.

Disposition of a patient after treatment of a hip fracture is largely dictated by the patient's functional status at the time of discharge. The abilities to ambulate and independently perform ADLs are two of numerous factors that help determine the discharge disposition of a patient. The ADLs required for functional independence include two groups: basic ADLs (BADLs) and instrumental ADLs (IADLs). BADLs include feeding, bathing, dressing, transferring, grooming, maintaining continence, and toileting. IADLs incorporate more advanced activities that allow for keeping an independent household such as shopping for food, cooking, banking, use of public transportation, and doing laundry. Multiple studies have shown that most patients who suffer a hip fracture lose functional independence, with 33% to 73% of patients regaining their preinjury function in BADLs and 21% to 48% of patients regaining their baseline capacity in IADLs. Poor prognostic indicators for return to prefracture function in both BADLs and IADLs after a hip fracture have been identified. These factors include patient age older than 85 years, low preinjury physical function, history of postoperative complication, one or more preexisting medical comorbidities, institutionalization on discharge, and living alone before injury.

After surgical treatment, 24% to 72% of patients are discharged to home. Of patients who lived in the community before sustaining a hip fracture, poor baseline cognitive function most strongly predicted being discharged to an institution for at least 6 months. A lack of baseline social supports before injury, such as family involvement or a caretaker, was also predictive of a patient being institutionalized at discharge for at least 6 months. Permanent institutionalization after a hip fracture has been associated with patient age older than 80 years, poor cognitive function, requiring assistance with ADLs, inadequate physical therapy, and lack of family support. A strong social support network, being married, and normal preinjury cognitive function are factors that have been found to be protective against institutionalization at discharge after treatment of a hip fracture. In addition, patients younger than 85 years of age, those independently ambulating at the time of hospital discharge, and those with three or fewer medical comorbidities are more likely to resume living independently after discharge.

Despite advances in medical care and surgical treatments of major fragility fractures, such as hip fractures, overall patient outcomes have not drastically improved over the past 40 years. The 1-year mortality rates after a hip fracture remain nearly 24%, and 30-day mortality rates approach 10%. As with other diagnoses, length of stay during the acute hospitalization for hip fractures has decreased over the past two decades, but patient outcomes have not improved. Readmission after discharge for hip fracture occurs more than with any other associated orthopaedic diagnosis, with rates estimated as high as 14.5% in 2011. Even with the development of new surgical implants and implant design improvements, implant failure is a common occurrence with hip fracture treatments and complication rates remain high. After the index surgery, 3% to 10% of patients will require a revision surgery due to implant or fixation failure. Similarly, mortality rates have not improved with the development of more novel surgical implants and techniques. When comparing cemented to noncemented hip hemiarthroplasty implants in the treatment of patients with femoral neck fractures, the mortality rates for patients undergoing noncemented hip hemiarthroplasty were lower only during the first 2 postoperative days compared with patients treated with cemented implants. Longer follow-up at 6 years showed no difference in the mortality rates between the two implant designs. Other studies comparing cemented to noncemented implants have shown no difference in mortality rates, pain scores, and functional outcomes such as independence levels at any point in time during a 2-year follow-up period. In addition, the more modern, noncemented, implants were found to have a higher rate of complications, such as subsidence related to fracture, than the cemented implant group. Although there is a better understanding of why hip fracture surgical fixations fail, the more novel implant designs and techniques have yet to improve patient outcomes.

Patients who present with a single fragility fracture, such as a hip fracture, will often sustain additional fragility fractures in the future. The risk factors that placed the patient at risk for the initial hip fracture remain present after treatment of the original injury, increasing the risk for future fractures. Patient factors such as history of a previous fracture, diminished bone mineral density, cognitive impairment, functional disability, decreased visual acuity, and the presence of sedating medicines create the perfect milieu for mechanical falls, resulting in subsequent fractures. The rate of secondary fractures in some populations has been estimated at 3% within 3 months and 9.2% within 2 years of the index hip fracture. These secondary injuries often include fractures of the wrist, hip, and vertebral column. Many of the factors placing a patient at increased risk for secondary injuries are difficult to modify. Even in the best-case scenario, where the orthopaedic surgeon can refer the patient to an orthopaedic osteoporosis clinic after a hip fracture, only 58% of patients were found to be on pharmacologic therapy for osteoporosis 6 months after discharge. When patients were referred to their primary care physician for osteoporosis therapy, the rate dropped to 29% at 6 months. Initiating evaluation of a patient after a fragility fracture by ordering a bone mineral density study in the orthopaedic clinic has been shown to improve osteoporosis evaluation and treatment rates. The failure to modify these risk factors places patients at continued risk for secondary fractures.

Socioeconomic Implications of Fragility Fractures

Fragility fractures represent an extraordinarily expensive diagnosis to care for both in terms of direct costs of care and also in terms of lost wages for those who are still employed. The high prevalence of these fractures and the prolonged healing time, combined with the high costs of care, make treatment of fragility fractures extraordinarily expensive. In the United States it has been estimated that 2 million osteoporotic fractures occur annually, with an estimated annual cost of $17 billion to $18 billion. By 2025 the direct costs from osteoporosis are expected to reach $25.3 billion in the United States. Hip fracture is the most costly of the osteoporotic fractures. In the United States there are approximately 330,000 hip fractures per year. The average length of stay is 6.4 days, which means that 2.1 million bed-days are occupied by hip fracture patients per year. The readmission rate for hip fracture is 14.5%, the highest readmission rate for any orthopaedic diagnosis. There is considerable variation in both the length of stay and readmission rates after hip fracture. Interestingly, this variation occurs in both academic medical centers and community hospitals and likely represents a significant cost to the healthcare system. These findings have resulted in hip fracture being the third most costly diagnosis in American medicine in 2012.

Hip fracture is expensive in many other ways. Hip fracture is frequently the sentinel event for an older individual's decline or death. Although the death may not be directly attributed to the hip fracture, the fracture nonetheless is associated with a 20% to 24% 1-year mortality rate in many studies. The specific causes of death are often very costly to care as well. Pneumonia is a common cause of readmission and death after hip fracture. Congestive heart failure and renal and urinary complications are also common. These are very costly diagnoses as well. After a fragility fracture, most patients are unable to return directly back to their prior living situation. This necessitates a stay in a subacute nursing care facility or occasionally an acute rehabilitation unit. These costs are typically somewhat less than the acute hospital stay but can account for the second most expensive aspect of care after a fragility fracture. Rehabilitation costs after discharge from a nursing facility and additional medical care add to the cost burden. If an individual is still employed he or she nearly always loses significant time from employment, which is quite costly to society as well.

For 20% or more of patients who have sustained a hip fracture or other major lower extremity fracture, loss of independence is an ongoing problem. This creates a significant cost burden on society and the family, as well as the patient. The costs of nursing home care are $66,000 to $140,000 per year. Assisted living care costs approximately half of that.

Is the Medical System Prepared for This Change?

Several traditional models of inpatient fracture care are prevalent in the United States and other countries. These include a multidisciplinary approach to the patient with a hip fracture. In the first traditional model, the patient with a hip fracture is admitted through the emergency department to an orthopaedic surgeon for care. Once admitted to the surgeon, a medicine specialist is requested to consult on the patient's fitness for surgery. The medicine specialist may be a family medicine physician, an internist, or a hospitalist physician. Rarely, a geriatrician is involved in the patient's care. Often the physician consulted is the patient's own primary care doctor who will need to see the patient before or after office hours. It is not uncommon that a cardiology consultation is requested if there is any cardiac history. This may result in a request for an echocardiogram as well. Once the patient has been medically cleared for surgery by the medicine physician, surgery is scheduled and performed on an urgent basis. Postoperatively, the hip fracture patient is typically managed by the surgeon with or without ongoing medicine consultation. Typically, the cardiologist will not follow the patient postoperatively unless there is an active cardiac condition. The patient is discharged from the hospital after discharge planning arrangements have been accomplished. The reported length of stay is 6.4 days with usual care in the United States.

Similarly, some patients with a hip fracture may be admitted to the medicine service preoperatively. This is particularly true of cases in which the patient is medically complex (many comorbidities) or medically unstable. The surgeon then becomes a consultant and performs the surgery when the patient has been medically optimized for surgery. In some cases, the patient will return postoperatively to the medicine service for postoperative management and discharge planning. The preceding two models of care are commonplace in the United States and have been in use for the past 50 years. Although multiple different disciplines or services may see the patient and treat him or her, the care is termed multidisciplinary as they tend to work “in silos” rather than in a concerted manner.

A newer model of care is termed the Geriatric Fracture Center or Rochester Model of Care . In this model, patients are co-managed throughout the hospital stay by a team of healthcare providers, including the orthopaedic surgeon, a geriatrician, nurses, therapists, and an anesthesiologist to provide interdisciplinary care ( Fig. 22.3 ). Interdisciplinary care involves healthcare providers working together seamlessly as a team with a focus on the patient and his or her needs. During the hospital stay, standardized order sets are used at each phase of care to reduce the likelihood of errors and adverse events. Such standard order sets include emergency department orders, admission orders, and postoperative orders. The nursing care plan is mapped out as a team so that the nursing care mirrors the standard order sets. All members of the team have identical expectations for the patient's hospital course. Discharge planning is done when the patient is admitted and expectations for a short length of stay are expressed by all members of the team to the patient and the patient's family. A focus on early surgical intervention is made in this model. It has been definitively shown that early surgery (<24 hours) reduces the risk of adverse events experienced by the hip fracture patient.

Fig. 22.3, Geriatric Fracture Center or Rochester Model of Care. ECG, Electrocardiogram; IV, intravenous; LMWH, low molecular weight heparin.

Additional important principles of this model are as follows: most hip fractures require surgical stabilization, patients should be made weight bearing as tolerated postoperatively, co-managed care results in reduced iatrogenic problems, and total quality management or “lean” business principles should be used to improve each stage of care. After surgery, it is important that patients be permitted to weight bear as tolerated on their surgical repair or replacement. Fortunately, hip fracture surgery has many options dependent on fracture pattern and location. In general, it is best that choice of procedure be the one that permits immediate weight bearing by the patient. Sometimes this may necessitate an alteration of the surgical plan. Additionally, with older adults, “single-shot” surgery is important. When older adults need revision procedures, they often experience tremendous loss of function and often will experience a complication. Therefore performing the surgery as a single procedure rather than a staged procedure is highly desirable and should be a goal of care for fragility fracture surgery. It has been shown that immediate weight bearing improves patient outcomes after hip fracture.

Another important consideration with the Geriatric Fracture Center care model is avoidance of delirium. Delirium is an acute confusional state characterized by inattention, fluctuating course, confusion, and disorientation that often occurs rapidly. It is commonly associated with hospitalization in older adults. It is more common in those who have preexisting dementia and can be challenging to differentiate from dementia. Delirium frequently occurs after a hip fracture and has been reported in up to 61% of cases. Mortality rates associated with delirium are high, with several studies estimating 6-month mortality rates to be at 14% and 22%, respectively. Outside of haloperidol for the agitated behavior of certain types of delirium there is no unique treatment, so it must be avoided if possible. Delirium can be avoided or reduced by performing surgery early, keeping tools for orientation (clocks, calendars) present in the room, having appropriate environmental stimuli (patients should retain their glasses and hearing aids), providing cognitive stimulation, facilitation of normal sleep schedules, early mobilization, appropriate pain control, oxygen delivery to the brain, proper fluid and electrolyte status, avoiding psychotropic drugs, proper nutrition, bowel and bladder function, early mobilization, treatment of symptoms of delirium, and prevention of postoperative complications. Delirium may present in either hyperactive or hypoactive form. The hyperactive variant is characterized by the patient being extremely agitated, crying out, trying to get out of bed, picking or pulling at the bedding or intravenous fluid lines, and hallucination. The hypoactive variant is more challenging to diagnose. Patients with hypoactive delirium may appear to be somnolent and difficult to arouse. When aroused, they typically will respond to the healthcare providers’ query with a short and sometimes appropriate response and then fall immediately back to sleep. Hypoactive delirium has a worse prognosis. It is often associated with aspiration pneumonia and therefore may cause the patient's demise. Overall, delirium increases the length of hospitalization, reduces the ability of patients to participate in their own rehabilitation, increases the risk of readmission, increases costs, and increases the risk of complications or death. There is a chronic variant of delirium that may persist long after the hospital stay. Once the patient has had delirium on a prior hospital stay, it is much more likely that he or she will have delirium on subsequent hospitalizations. Delirium avoidance includes avoiding harmful medications such as diphenhydramine, meperidine, benzodiazepines, and histamine type 2 (H2) blockers.

Published outcomes of this care model have shown a lower than expected length of hospital stay, reduced complications, reduced readmissions, and reduced costs compared with usual care models. In the era of healthcare reform, this combination of improved quality and safety with reduced costs makes this care model attractive to many hospitals to adopt.

Changes in the care model and payment model have been associated with improved patient outcomes coupled with reduced costs in the National Health Service in the United Kingdom. The Best Practice Tariff has been implemented for fragility hip fractures. Suggested actions for healthcare professionals in this program include the following :

  • Time to surgery within 36 hours from arrival in emergency department

  • Admitted under the joint care of a consultant geriatrician and a consultant orthopaedic surgeon

  • Admitted using an assessment protocol agreed on by geriatric medicine, orthopaedic surgery, and anesthesia

  • Assessed by a geriatrician in the preoperative period within 72 hours of admission

  • Postoperative geriatrician-directed multiprofessional rehabilitation team

  • Fracture prevention assessments—falls and bone health

To achieve the full hospital reimbursement, all of these assessments must be performed on each patient. This approach to system management has resulted in reduced mortality rates at 30 days and 1 year for those who achieved the Best Practice Tariff. It is also noted that this approach is very similar in content to the Geriatric Fracture Center model of care.

A few additional comments are appropriate here. There is an inverse relationship between quality of care and cost of care. Thus it is less costly to care for a fragility fracture well than to care for it poorly. Additionally, orthopaedic surgeons should be focusing on improvements in the system of care rather than on the traditional focus on specific implants used in care as a means of improving patient outcomes. Only with system changes will we be able to improve quality of care to older adults with a fragility fracture.

Secondary Fracture Prevention: Dietary Supplementations and Medical Therapies

Patients who sustained a fragility fracture are at markedly increased risk of developing a subsequent fracture. Patients with a fragility fracture should be advised of their diagnosis of osteoporosis. Although simple to carry out, this is not often done in practice. Orthopaedic surgeons are typically the first medical care providers to treat patients with a fragility fracture and should discuss the diagnosis of osteoporosis.

Secondary prevention of fracture involves a two-pronged approach to the patient. The first should be postfracture osteoporosis management and the second is fall prevention. These two approaches are covered in some detail in the following sections.

Vitamin D and Calcium

After a fragility fracture, common causes of secondary osteoporosis should be sought. The most common cause of secondary osteoporosis is vitamin D deficiency or insufficiency. Testing for vitamin D insufficiency or deficiency can easily be accomplished by ordering a small number of laboratory tests when the patient is initially hospitalized. These include a calcium level, parathyroid hormone (PTH) level, and a 25-OH vitamin D level. A low 25-OH vitamin D level combined with a lower value of serum calcium will establish the diagnosis of vitamin D deficiency or insufficiency. There is some dispute as to what level constitutes deficiency and what level constitutes insufficiency in the published literature. A deficient state implies that the patient is experiencing some symptoms of the condition, whereas the insufficient state may be asymptomatic. Frequently, the PTH level will also be elevated as a marker of vitamin D deficiency. With this same set of laboratory tests, a diagnosis of primary hyperparathyroidism can be established. This would include an elevated calcium and elevated PTH level. A thyroid-stimulating hormone (TSH) level is another reasonable laboratory test to evaluate for hyperthyroidism. Other common causes of secondary osteoporosis include prolonged anticonvulsant usage, immobilization, long-term heparin, hypogonadism in men, glucocorticoid use for more than 6 months, renal failure, Parkinson disease, and use of antiretroviral medications in the treatment of human immunodeficiency virus (HIV). The more complex the cause of the secondary osteoporosis, the more the patient would benefit from assessment and treatment in a metabolic bone clinic. Most hip fracture patients will require supplementation with vitamin D to help them heal their new fracture. Table 22.1 offers guidance on management of vitamin D deficiency and insufficiency.

Table 22.1
Recommendations for Vitamin D Supplementation
25-OH Vitamin D Level Dose (IU) Type Frequency
0–10 ng/dL 50,000 Vitamin D 2 Three times per week
11–20 ng/dL 50,000 Vitamin D 2 Twice per week
21–32 ng/dL 50,000 Vitamin D 2 Once a week
Maintenance 2000 Vitamin D 3 Daily

It is recommended to recheck the level of 25-OH vitamin D after 6 to 8 weeks of the described treatment to ensure adequate repletion of the patient's vitamin D level. It should be remembered that vitamin D is a fat-soluble vitamin that is widely distributed and metabolized in the human body. Therefore it can take a prolonged treatment period to correct a deficient or insufficient state. There is much controversy about the correct maintenance level to use. However, when treating patients who have already experienced a fragility fracture, correction of this abnormal state will benefit their healing and help prevent secondary fractures.

Inadequate dietary consumption of calcium is common. The appropriate total consumption of calcium should be 1000 to 1300 mg per day. This includes the dietary source plus supplemental calcium. Calcium alone is not protective for fracture.

Bisphosphonate Therapy

Bisphosphonates are a commonly used first-line therapy for treatment of postfracture osteoporosis. Bisphosphonates are analogues of hydroxyapatite and bind to bone permanently. They typically have very long half-lives of 3 to 11 years. They inhibit osteoclast-mediated resorption of bone. They also increase osteoclast apoptosis. Bisphosphonates inhibit bone remodeling but not bone healing. It is safe to start the oral bisphosphonate therapy (alendronate, risedronate) immediately after fracture on a patient who is bisphosphonate naïve. It will take approximately 6 months after oral dosing for the patient to develop adequate bone levels of bisphosphonate to prevent secondary fractures. Bisphosphonates have been shown to be extremely effective at preventing hip fracture, vertebral fracture, and other types of fracture. However, oral dosing of bisphosphonates can be problematic. Upper gastrointestinal side effects (reflux, esophagitis, ulcers) are among the most commonly reported side effects for oral bisphosphonates but, when used correctly, the incidence of these side effects is very low. Unfortunately, poor compliance with bisphosphonate therapy has been reported, with upward of 50% of patients stopping the medicine within the first 6 months. Part of the problem probably stems from its route of administration, which involves drinking the tablet with a full glass of water while sitting in an upright position for 30 minutes to 1 hour. The medication is only appropriate in patients who have fairly normal renal function. Patients with advanced renal disease, esophageal disorders (achalasia, Barrett esophagus, esophageal strictures, esophageal varices), or who cannot sit upright for an hour after taking the medication should be considered for alternative therapy.

Bisphosphonates can be administered intravenously (zolendronic acid) on a yearly basis and this route of administration is not associated with negative upper gastrointestinal side effects. It is not recommended for patients with advanced renal disease. Intravenous administration of bisphosphonates can be associated with a short duration of a flulike illness in 32% of patients within 72 hours of their first dose. Patients should be advised that these flulike symptoms can be treated with antipyretics and that their subsequent doses will have a reduced incidence of this side effect—6.6% and 2.8% incidence on the second and third dose, respectively.

Bisphosphonates are the preferred treatment to prevent glucocorticoid-induced osteoporosis and are the first-line treatment for postfracture osteoporosis management. Some patients, as mentioned earlier, may benefit from other types of treatment.

Certain side effects of bisphosphonates are very concerning. A small percentage of patients treated with bisphosphonates for a prolonged period (>5 years) may develop an atypical fracture of the femur. The atypical fracture is seen between the lesser trochanter and the supracondylar region of the femur. It typically has a simple fracture pattern such as transverse or short oblique and may have a “medial spike.” There may be prodromal symptoms, such as aching in the thigh, which precede the fracture. The fracture always initiates from the tensile, lateral, side of the femur and propagates medially. There may be a lateral periosteal reaction. In some cases a black line appears through the lateral cortex, and this has been called the “dreaded black line.” A full list of criteria for the atypical fracture has been nicely described by the ASBMR task force in 2010 and updated in 2014. Treatment of the atypical fracture includes stopping the bisphosphonate therapy immediately, reduction and intramedullary nailing of the fracture, and managing delayed healing in some cases with anabolic therapy such as the PTH analogue teriparatide. The contralateral femur should be closely followed as it may also fracture. Prophylactic nailing of the contralateral femur is controversial and should only be undertaken if there is a high probability of fracture such as the presence of the “dreaded black line on the lateral cortex.”

Another side effect is osteonecrosis of the jaw seen most commonly in patients with cancer or in patients with compromised immune systems. If osteonecrosis is to occur, it most typically does so in those who also have preexisting dental disease, poorly fitting dentures, or recent history of a dental procedure. Treatment includes immediate discontinuation of the bisphosphonate.

Selective Estrogen Receptor Modulators

Selective estrogen receptor modulators (SERMs) are serum estrogen receptor modulators. They are a second-line, hormonally based therapy used in postmenopausal women with osteoporosis in whom bisphosphonate therapy is contraindicated. These medications stimulate the estrogen receptor in bone but are associated with antiestrogen effects in the breast. It is considered an antiresorptive therapy. SERMs are associated with an increased incidence of venous thromboembolism (VTE) for the first 4 months of therapy. Other side effects include hot flashes, leg cramps, and peripheral edema. Raloxifene is the most commonly used medication in this class. These are rarely used in current practice.

Calcitonin

Calcitonin is a hormone that stimulates bone formation. Based on recent recommendations, it has no place in osteoporosis management at this time.

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