In the first part of this two-part series on fragility fractures and bone health, we examined the biologic processes and therapeutic considerations involving nutrition, supplementation and activity. In this concluding second part, we turn to issues in diagnosis and treatment for patients with fragility fractures and other conditions related to osteoporosis.

The evaluation of fragility fracture patients, especially those who are hospitalized, calls for choices and decisions involving laboratory studies. Previously we described laboratory tests that should be obtained preoperatively for patients who require operative fracture fixation. Other specialized tests, including those ordered to determine the etiology and extent of osteoporosis, are best obtained 6 to 8 weeks following a patient's fracture. Many experts now feel that tests such as those for 25-hydroxy (OH) Vitamin D, parathyroid hormone (PTH), thyroid-stimulating hormone (TSH), serum protein electrophoresis (SPEP), and testosterone levels are best done at this postfracture time period, when a more accurate value can be ascertained.

When vitamin D levels are obtained at the time of a patient's admission for fracture, they should be accomplished preoperatively, since studies indicate that vitamin D values decrease significantly following orthopaedic hip surgery of any kind. The same applies to obtaining dual-energy x-ray absorptiometry (DXA) scans, primarily because of the physical difficulty experienced by the patient during a DXA scan in the immediate post-fracture setting.

This brings us to a discussion of treatment for bone health and osteoporosis in older adult patients with fragility fractures that may encompass the hip, vertebrae, proximal humerus, pelvis, or distal radius. In determining whom to treat and which agent to use, we must recall that most fragility fractures occur in patients whose official DXA scan T-score, in either the hip or spine, is consistent with osteopenia rather than osteoporosis. Therefore, realizing the devastating sequelae of hip fractures—significant morbidity, loss of independence, and increased mortality—most bone health experts, with the support of the National Bone Health Alliance Working Group, now assume that any patient with a fragility hip fracture has osteoporosis by definition, with or without a DXA scan. In addition, patients with fractures in the other areas mentioned who have DXA scans consistent with osteopenic values and are at increased risk for fracture by virtue of their Fracture Risk Assessment Tool, or FRAX, score should also be considered to have osteoporosis, and therefore in need of treatment. FRAX, the important computerized clinical decision-making tool developed by John A. Kanis of the University of Sheffield and popularized by the World Health Organization, evaluates patients in regard to demographic data and medical history, including smoking, alcohol consumption, fracture, history of hip fracture in a parent, rheumatoid arthritis, glucocorticoid therapy, secondary osteoporosis and, optionally, a hip DXA score.

The FRAX instrument can be accessed online (https://www.shef.ac.uk/FRAX/tool.jsp) and is specific to the patient's country of origin. The computerized score estimates fracture risk to be significant and, therefore, consistent with osteoporosis if the 10-year risk of hip fracture is equal to or greater than 3 percent and the risk of other osteoporotic fracture is equal to or greater than 20 percent—thus indicating the need for treatment in patients with fragility fractures other than the hip. This tool is extremely helpful, for example, in deciding whether to treat low bone mass in a patient who sustains a wrist fracture during the 6th decade, due to concerns about adverse effects from the use of long-term osteoporosis treatment.

When considering pharmacologic treatment options, we now have a myriad of choices, most of which are related to antiresorptive therapy targeting the inhibition of osteoclast function. In this regard, the most common and well-recognized medication class is the bisphosphonate (BP) group, which includes alendronate (Fosamax), available for about 20 years in the United States, risedronate (Actonel), ibandronate (Boniva), and zoledronate (Reclast). Their clinical efficacy, like that of other FDA-approved anti-osteoporosis drugs, has been proven by clinical trials indicating a decrease in subsequent hip and vertebral body fractures, although long-term use trials have indicated a decrease in only vertebral fractures.

Given the fact that currently alendronate is the only such drug available as a generic, it is most frequently used in the treatment of osteoporosis, for cost reasons. It, as well as risedronate and ibandronate, can be given orally on a weekly basis, as opposed to the original daily dosage, and ibandronate may also be given monthly; alternatively an intravenous form may be given every 3 months. Oral administration of BPs should be accomplished early in the morning on an empty stomach, utilizing a full glass of water with the patient upright for 30 to 45 minutes thereafter to prevent gastroesophageal irritation.

Zoledronate has the benefit of being an intravenous infusion required only once yearly. While a patient may experience general malaise and musculoskeletal symptoms for a day or two following its infusion, this drug is associated with not only a decrease in fractures but also a general decrease in overall mortality. Its yearly dosing makes it an ideal option for patients who cannot tolerate oral BPs or for the very elderly who might have significant adherence problems.

Although excellent results have been obtained with BPs, their use should be avoided in patients with kidney disease. Should this be an issue, one can turn to denosumab (Prolia), another antiresorptive drug, which can be used in the presence of kidney disease and represents a new-wave approach to osteoporosis disease control. Acting like many of the anticytokine agents used in chronic inflammatory conditions, this agent is a monoclonal antibody against RANK-L, which blocks the normal osteoblastic production of that ligand and its resultant stimulation of osteoclast activity, which predominates in osteoporosis. It also has the benefit of subcutaneous dosing required only every 6 months, although it must be provided by a physician or advanced practice provider—ie, a nurse practitioner, advanced practice nurse, or physician assistant.

There has been a longtime concern in the orthopaedic community about the early postfracture use of BPs due to the possibility that they may inhibit fracture healing. Evidence to date shows that while decreased healing has been seen in animal studies there are no studies corroborating those findings in humans. Nevertheless, because immediately following a fracture most of the BP drug migrates to the fracture site instead of the skeleton as a whole, initiation of treatment is best accomplished at 6 to 8 weeks following the fracture, when laboratory testing and DXA scans are obtained.

Clinical estrogen supplementation is no longer advised for osteoporosis treatment due to the frequency of significant cardiovascular and malignancy adverse events, but the estrogen-like drug raloxifene (Evista) may be used in treating some women with less severe bone mass loss, although menopausal symptoms are not abated by its use. In addition, raloxifene has been shown to affect only the rate of vertebral fracture occurrence. Calcitonin, while it may be effective in decreasing the acute pain of vertebral fractures in some cases, is no longer considered a significant option for osteoporosis treatment.

Although this discussion has applied to drugs used to inhibit osteoclast activity, one anabolic agent currently available in the United States, parathyroid hormone (1-34) (PTH) as teriparatide (Forteo), may significantly increase bone mass and strength. Not only has it been shown to decrease the occurrence of hip and spine fractures, but animal studies have also indicated enhanced fracture healing and spine fusion rates with its use. The drug is given by a self-administered daily subcutaneous injection, thus producing an intermittent daily increase in PTH with its resultant anabolic effect, the opposite of the decrease in bone mass as seen in multiple skeletal areas in hyperparathyroidism, where a constant elevated amount of hormone is present.

Due to the finding of osteosarcoma in a rat study prior to its clinical use, despite no statistical evidence of malignancy induced by its use in humans, the total duration of lifetime use for teriparatide is limited to 2 years cumulative—with  its use allowed for multiple months at different periods of time. Thus, teriparatide may be prescribed for a number of months for fracture patients who are unable to be treated with BPs, for those in whom antirestorative treatment has failed, and for patients with extensive osteoporosis who would benefit from an early anabolic effect—possibly followed by the use of a BP. Also, patients with pelvic stress fractures may benefit from its enhanced healing effects, which has caused some orthopaedists to employ its use in the treatment of some tibial and other long bone nonunions. Also, PTH has an application in some patients who need augmented bone strength prior to spinal surgery and in some who may require it postoperatively to facilitate fusion and improve instrument fixation. While cost has been an issue with teriparatide, programs are available to subsidize its cost for patients with specific clinical conditions.

Andrew D. Bunta, MD, is on the faculty of Northwestern University Feinberg School of Medicine, Chicago, and is chair of the AOA Own the Bone Multidisciplinary Advisory Board. Joseph M. Lane, MD, is professor of Orthopaedic Surgery and chief of the Metabolic Bone Disease Service, Hospital for Special Surgery, New York, N.Y.