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.
But even in chronic kidney disease, many fractures are due to postmenopausal or agerelated osteoporosis, and estrogen-deficiency osteoporosis is the most common cause of fragility fractures overall.1–3 Osteoporosis can be diagnosed only after other causes of skeletal fragility have been ruled out. And how to diagnose and treat osteoporosis in the most severe stage of kidney disease is a matter of opinion, as we have almost no data to guide us.
Nevertheless, in the pages that follow, I will outline my admittedly opinion-based approach to diagnosing and managing the causes of fragility fractures in patients with chronic kidney disease.
T SCORES DO NOT DISTINGUISH THE CAUSES OF FRAGILITY
The most common cause of fragility fractures is osteoporosis due to estrogen deficiency.1–3 But since many other medical conditions can lead to osteoporosis, simple diagnostic criteria have been difficult to find.
Before 1994, the diagnosis of osteoporosis was made on the basis of low-trauma fractures.4 Now, we use the World Health Organization criteria,5 based on bone mineral density T scores:
- Normal—a T score of −1.0 standard deviations or higher
- Osteopenia—a T score of less than −1.0 but higher than −2.5
- Osteoporosis—a T score of −2.5 or less
- Severe osteoporosis—a T score of −2.5 or less with a fragility fracture.
However, fractures can also be due to metabolic bone diseases that are not osteoporosis, including renal bone diseases.6–7 While a low T score or a fracture provides a working diagnosis of osteoporosis, it does not help distinguish the different types of osteoporosis and nonosteoporotic metabolic bone diseases. For example, osteomalacia and osteogenesis imperfecta can also cause fragility fractures and can be associated with low bone density. Using these criteria to define osteoporosis is even more problematic in patients with chronic kidney disease.
FIVE STAGES OF CHRONIC KIDNEY DISEASE
The National Kidney Foundation8 classifies the severity of chronic kidney disease on the basis of the glomerular filtration rate (GFR), as measured by 24-hour urine for creatinine clearance, or as estimated by the Cockcroft-Gault equation or, preferably, the Modification of Diet in Renal Disease (MDRD) equation (calculators are available at www.kidney.org/professionals/kdoqi/gfr_calculator.cfm):
- Stage 1—GFR 90 mL/minute/1.73 m2 or higher
- Stage 2—GFR 60 to 89
- Stage 3—GFR 30 to 59
- Stage 4—GFR 15 to 29
- Stage 5—GFR lower than 15, or if the patient is on dialysis. (Another stage, called 5D, was added to the list to denote patients on dialysis, since the metabolic derangements in bone and systemic biology may differ between patients on dialysis vs those not on dialysis.)
This staging system is relevant to the discussion of bone fragility that follows.
CHRONIC KIDNEY DISEASE IS COMMON IN THE ELDERLY
The third National Health and Nutrition Examination Survey9 found that, at least as estimated by the Cockcroft-Gault equation, the GFR declines with age, so that by the age of 70 at least 20% of the US population has stage 4 or 5 chronic kidney disease.
Although the Cockcroft-Gault and MDRD equations may yield lower GFR values in the general population than one would get by measuring creatinine, inulin, or iothalamate clearance,10,11 the point is that both osteoporosis and chronic kidney disease are common.
THE GAMUT OF RENAL OSTEODYSTROPHY
In kidney failure (stage 5 chronic kidney disease), all forms of renal osteodystrophy may be associated with fragility fractures. Renal osteodystrophy can be defined by quantitative bone histomorphometry.12,13 The systemic conditions that may be associated with the bone disease and systemic vascular disease (chronic kidney disease–mineral and bone disorder) are characterized by one or more of the following14:
- Abnormalities of calcium, phosphorus, parathyroid hormone, or vitamin D metabolism
- Abnormalities in bone turnover, mineralization, volume, linear growth, or strength
- Vascular or other soft-tissue calcification.
The National Kidney Foundation14 classifies renal osteodystrophy on the basis of:
- Turnover—high, normal, or low
- Mineralization—normal or abnormal
- Volume—high, normal, or low.
Although this system helps us understand these diseases better, it does not provide a working diagnosis of osteoporosis.14
