Fragility fractures in chronic kidney disease: An opinion-based approach
ABSTRACTWhen a patient with chronic kidney disease suffers a fragility fracture, a key question is whether the patient has osteoporosis or, instead, renal osteodystrophy. Bone densitometry does not help in this distinction: biochemical tests, and sometimes also bone biopsy, are needed. However, even if the patient has osteoporosis, we have little evidence to guide our treatment decisions in cases of advanced chronic kidney disease.
KEY POINTS
- If the patient’s glomerular filtration rate (GFR) is at least 30 mL/min/1.73 m2 and if no biochemical test results suggest renal osteodystrophy, osteoporosis can be diagnosed if the T score is less than −2.5 or if the patient has had a fragility fracture. These criteria can also probably be applied, though with less certainty, if the patient’s GFR is as low as 15.
- If the patient’s GFR is less than 15 or if he or she is on dialysis, biochemical profiling often cannot distinguish among the heterogeneous forms of renal bone disease. In some cases of severe chronic kidney disease with fractures, bone biopsy is needed to rule out renal osteodystrophy and to diagnose osteoporosis by exclusion.
- In the author’s opinion, in patients with severe chronic kidney disease and fractures who have “osteoporosis” by exclusion, off-label use of bisphosphonates is an option, but only after very careful consideration.
WHAT IS OSTEOPOROSIS?
In an attempt to define osteoporosis by a pathophysiologic mechanism, the National Institutes of Health15 have held two consensus conferences and have stated that “osteoporosis is a skeletal disorder characterized by impairment in bone strength predisposing a person to an increased risk of fracture. Bone strength primarily reflects the integration of bone density and bone quality.”15 However, the consensus statement also does not provide a working diagnosis of osteoporosis—one that clinicians can apply to management decisions, and one that is also accepted by the US International Classification of Disease codes for reimbursement purposes.
The 1994 World Health Organization criteria offer the most pragmatic operational definition of osteoporosis, and they can be applied in both men and women, as well as in younger patients with medical conditions associated with increased risk of low-trauma fracture.5,16 Although the main purpose of these criteria was to advise international health authorities of the potential future economic impact of osteoporosis, the T score also became the pragmatic diagnostic threshold for defining normal, osteopenia, and osteoporosis in clinical practice.
The T score also calls attention to an important observation: of people who have fractures and subsequently undergo bone densitometry, more are found to have osteopenia than osteoporosis. The reasons are that there are more people with osteopenia than osteoporosis,17,18 and many other factors independent of low bone mineral density contribute to bone strength.19,20
How is osteoporosis diagnosed in stage 1–3 chronic kidney disease?
In patients with chronic kidney disease who develop fragility fractures, the reasonable question is: Is the cause of the fracture osteoporosis or some other metabolic bone disease associated with chronic kidney disease?
The National Kidney Foundation guidelines14 say that the diagnosis of osteoporosis can be established in patients with stage 1, 2, or 3 chronic kidney disease on the basis of either of the World Health Organization criteria, ie, a T score of −2.5 or lower or fragility fractures, as in the postmenopausal population, as long as there are no biochemical abnormalities that suggest chronic kidney disease–mineral and bone disorder.
How is osteoporosis diagnosed in stage 4 or 5 chronic kidney disease?
The answer is neither straightforward nor clearly defined in severe (stage 4 or 5) chronic kidney disease.
In stage 5 and especially in patients on dialysis, the derangements in bone and mineral metabolism become serious enough to impair bone strength and increase the risk of lowtrauma fractures. The risk of hip fracture in stage 5 may be four times higher than in agematched controls.21–24
Adynamic, severe hyperparathyroid bone disease as well as osteomalacia can be associated with a higher risk of fragility fractures than in aged-matched controls in population studies of postmenopausal women or elderly men. These are bone fragility conditions that are not osteoporosis but that can mimic osteoporosis by the World Health Organization criteria.
Thus, when a patient in stage 5 has severe fragility fractures that by themselves may be life-threatening, it is reasonable to ask if the drugs that reduce the risk of fractures in many other osteoporotic conditions (postmenopausal, steroid-induced, elderly male osteoporosis, after solid organ transplantation) can also be used in patients with advanced chronic kidney disease.
The diagnosis of osteoporosis in these patients has no universally accepted criteria. The diagnosis is best suggested by excluding other forms of renal osteodystrophy by quantitative histomorphometry or by attempting to classify the form of renal osteodystrophy by noninvasive means of assessing bone turnover, mineralization, and volume. However, we lack clinical tools to make these distinctions in individual patients.
While many promising radiologic techniques that examine bone microarchitecture offer hope of being able to define turnover, mineralization, and volume noninvasively in severe chronic kidney disease, they are investigational and unproven at this time in discriminating between renal osteodystrophy and osteoporosis.6,25–27 As we increase our understanding of the relationships between turnover, mineralization, volume, and bone strength, these noninvasive imaging technologies may become the means to correlate turnover, mineralization, and volume to bone strength and open up an entirely new way to classify skeletal strength.
In the meantime, the clinician is left with quantitative bone histomorphometry (which requires biopsy) and biochemical markers of bone turnover to characterize the bone disease that may be responsible for low-trauma fractures in stage 5 chronic kidney disease. The clinician should first use biochemical markers before bone biopsy to distinguish the form of renal osteodystrophy, as this distinction may be able to prevent unnecessary biopsy.
