Osteoporosis in patients with chronic kidney disease: Diagnosis and evaluation

INTRODUCTION — Osteoporosis is a common disease that is characterized by low bone mass with microarchitectural disruption and skeletal fragility, resulting in an increased risk of fracture, particularly at the spine, hip, wrist, humerus, and pelvis [1]. It is difficult to diagnose osteoporosis in the setting of chronic kidney disease (CKD). This is particularly relevant for the aging population, where fragility fractures, reduced glomerular filtration rate (GFR), and low bone mineral density (BMD) are more prevalent.

There are multiple reasons why this differentiation is important, not the least of which is that management of osteoporosis differs vastly from treatment of other bone diseases in patients with CKD.

This topic will review the diagnosis and evaluation of osteoporosis in patients with CKD. The management of osteoporosis in CKD, as well as the pathogenesis, diagnosis, and management of other aspects or mineral and bone disorders (MBD) in patients with CKD are reviewed elsewhere.

●(See "Osteoporosis in patients with chronic kidney disease: Management".)

●(See "Overview of chronic kidney disease-mineral and bone disorder (CKD-MBD)".)

●(See "Evaluation of renal osteodystrophy".)

●(See "Management of secondary hyperparathyroidism in adult nondialysis patients with chronic kidney disease".)

●(See "Management of secondary hyperparathyroidism in adult patients on dialysis".)

CKD-MBD DEFINITION — Changes in mineral metabolism and bone structure develop early in the course of chronic kidney disease (CKD) and worsen with progressive loss of kidney function. CKD-MBD (mineral and bone disorder) includes [2]:

●Abnormalities of calcium, phosphorus, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and vitamin D metabolism

●Abnormalities in bone turnover, mineralization, volume, linear growth, or strength

and/or

●Vascular or other soft tissue calcification

The more severe forms of CKD-MBD define the systemic nature of phosphorus and bone metabolism in progressive stages of CKD in order to link these changes to the vascular calcification that is the major cause of mortality in CKD. (See "Overview of chronic kidney disease-mineral and bone disorder (CKD-MBD)".)

Renal osteodystrophy is now a term confined to the spectrum of bone histomorphometry in CKD. Renal osteodystrophy includes hyperparathyroid-mediated, high-turnover bone disease or osteitis fibrosa cystica; adynamic bone disease; osteomalacia; and mixed uremic osteodystrophy. (See "Evaluation of renal osteodystrophy".)

It is difficult to diagnose osteoporosis in the setting of CKD-MBD. Patients with CKD may have osteoporosis either before or after developing kidney disease. Osteoporosis, a term that includes major alterations in bone quality, is probably a universal feature accompanying bone disease in all forms of renal bone disease (table 1).

FRACTURE RISK IN CHRONIC KIDNEY DISEASE

Magnitude of the problem — End-stage chronic kidney disease (CKD) is associated with an increased risk of fragility (low trauma) fractures [3-5]. The risk of fracture-related mortality increases with the severity of CKD [3,6].

In most [5,7-16], but not all [17], studies, more moderate degrees of renal insufficiency have also been associated with an increased fracture risk. In a systematic review and meta-analysis of studies evaluating fracture risk in adults with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m², there was a significant increase in hip (relative risk [RR] 2.36, 95% CI 1.64-3.39) and nonvertebral (RR 1.47, 95% CI 1.15-1.88) fractures compared with eGFR ≥60 mL/min/1.73 m², and fracture risk increased with decreasing eGFR [18]. In a large health care database study from Canada, decreasing eGFR was associated with an increase in the three-year cumulative incidence of fracture (hip, forearm, pelvis, proximal humerus) in females and males [13]. In females >65 years of age, the incidence of fracture was 4.3, 5.8, 6.5, 7.8, and 8.6 percent for eGFR thresholds of ≥60, 45 to 59, 30 to 44, 15 to 29, and under 15 mL/min/1.73 m². The incidence for males was 1.6, 2, 2.7, 3.8, and 5 percent, respectively.

The exact mechanism for this greater fracture risk in CKD is not clearly established, but there are biological changes in bone metabolism that render the skeleton in patients with progressive CKD (glomerular filtration rate [GFR] stages G3 to G5 (table 2)) more fragile. These changes, including phosphorus retention, secondary hyperparathyroidism, chronic acid loads, elevated fibroblast growth factor 23 (FGF23), or sclerostin overproduction, may contribute independently or collectively to the increased fracture risk that is seen in GFR stages G3 to G5 [2,19-22]. In addition, the greater risk of falls in this population with sarcopenia and frailty may also contribute to the greater fracture risk [7]. Other risk factors include glucocorticoid use, hypogonadism, hyperprolactinemia, poor nutrition, vitamin D deficiency, and inactivity [23].

Assessment of fracture risk — The assessment of fracture risk includes evaluation of clinical risk factors for fracture (table 3), and, in most patients, measurement of bone mineral density (BMD) using dual-energy x-ray absorptiometry (DXA). (See 'Bone mineral density: DXA' below.)

Fracture risk assessment tool — In 2008, a World Health Organization (WHO) task force introduced a Fracture Risk Assessment Tool (FRAX), which estimates the 10-year probability of hip fracture and major osteoporotic fracture (hip, clinical spine, proximal humerus, or forearm) for untreated patients between ages 40 and 90 years using easily obtainable clinical risk factors for fracture (table 3) and femoral neck BMD (g/cm², using DXA), when available. This fracture risk assessment tool is reviewed in detail elsewhere. (See "Osteoporotic fracture risk assessment", section on 'Fracture risk assessment tool'.)

FRAX does not include any adjustment of risk according to GFR. Although GFR (usually eGFR) was measured in some of the nine population studies used to construct the FRAX model, the sample size was not statistically powerful enough to validate the independent contribution of reduced GFR on fracture risk. In subsequent studies, FRAX was able to predict fracture in patients with CKD, the majority of whom had CKD stages G3a and G3b [24,25].

In clinical practice, FRAX may be applied to patients with CKD. Just as one may need to incorporate falls or frequency of falls (which were also not captured in FRAX) into a clinical judgment when utilizing FRAX, the clinician should also consider adjusting the absolute fracture risk to a higher level in patients with eGFR stages G3b to G5 (table 2) [8,9,26-28].

Bone mineral density: DXA — For patients with CKD, eGFR ≥30 mL/min/1.73 m², and risk factors for fracture, BMD (dual-energy x-ray absorptiometry [DXA]) testing may be used to assess fracture risk. Although BMD testing is not routinely performed to assess fracture risk in patients with CKD and eGFR <30 mL/min/1.73 m², it may be obtained in selected patients with eGFR <30 mL/min/1.73 m² who have fragility fracture and no evidence of CKD-MBD (mineral and bone disorder), including renal osteodystrophy, particularly when osteoporosis therapy is being considered [29]. In these selected patients, measurement of BMD (hip and lumbar spine) at baseline and two years after osteoporosis therapy may also be helpful for monitoring response to therapy. (See "Osteoporosis in patients with chronic kidney disease: Management", section on 'Monitoring therapy'.)

These suggestions are largely consistent with 2017 KDIGO guidelines (Kidney Disease: Improving Global Outcomes) and the 2021 CKD-MBD working group consensus statement from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) [29,30] and are based on observational studies described below.

Measurement of BMD by DXA is routinely used to diagnose osteoporosis and assess fracture risk in the general population. Many studies in the general population have demonstrated that low BMD is associated with an increased risk of fracture. Although BMD is also lower in patients with CKD who fracture, it is unclear if BMD by DXA can be used to predict fracture in patients with the most advanced CKD (table 1) [7]. Prospective studies in patients with end-stage CKD (particularly, G5D) are required to address this question. (See "Osteoporotic fracture risk assessment", section on 'Bone mineral density'.)

●Predialysis CKD – In cross-sectional studies, BMD by DXA has been shown to be lower in patients with predialysis CKD who fracture compared with those who do not [31-33]. In one study, for every standard deviation decrease in lumbar spine, total hip, femoral neck, and ultradistal radius BMD by DXA, there was a significant increase in the risk of fracture (odds ratios [ORs] 1.93, 1.65, 1.86, and 2.29, respectively) [34].

●Dialysis dependent – BMD is also lower in dialysis-dependent patients who fracture, as illustrated by the findings of a meta-analysis of six cross-sectional studies, which included 683 patients on dialysis [35]. Compared with patients without fracture, patients with fracture had significantly lower BMD at the lumbar spine (mean difference -0.44, 95% CI -0.8 to -0.08) and radial sites (one-third radius; mean difference -0.75, 95% CI -1.38 to -0.12), but not at the femoral neck (-0.5, 95% CI -1.08 to 0.08).

In a subsequent study of Japanese dialysis patients, low hip BMD (DXA) was predictive of any type of incident fracture when the parathyroid hormone (PTH) was below the median value (204 pg/mL). However, the relationship between hip BMD and fracture was not significant if the PTH was above 204 pg/mL [36].

In patients with advanced CKD and elevated PTH levels, the bone density is lost primarily from the cortical bone, and it may be increased in the cancellous bone. Bone density (DXA) in the cortical bone of the radius or hip is generally lower compared with the normal reference range, but the spine bone density (cancellous bone) may be within the normal range [37].

DXA is unable to predict the type of bone lesion in dialysis-dependent patients [26,38,39]. The quantitative bone histomorphometric classification of renal bone diseases (eg, renal osteodystrophy) includes a heterogeneous group of bone diseases, all of which may have low T-scores and fragility fractures [40,41]. In addition, the interpretation of DXA may be confounded by the presence of extraosseous calcification and focal areas of osteosclerosis, which may lead to artifactual increase in BMD.

●Limitations of DXA – Although DXA is the most commonly used technique to assess BMD in patients with and without CKD, it has some limitations. DXA measures areal BMD, rather than volumetric BMD. In addition, it cannot distinguish between cortical and cancellous bone, and it cannot assess bone microarchitecture or bone turnover. Thus, new technologies (high resolution microcomputed tomography [microCT] and micromagnetic resonance imaging [microMRI], hip structural analysis, finite element analysis) have been developed that allow noninvasive, three-dimensional evaluation of bone microarchitecture. There are few data evaluating these techniques in patients with CKD [42], and they are not available in most clinical settings. (see "Osteoporotic fracture risk assessment", section on 'New and emerging technologies')

DIAGNOSIS — In the general adult population, the clinical diagnosis of osteoporosis is made in one of two ways: the presence of a low trauma fracture independent of the prevailing bone mineral density (BMD) or, in the absence of a preexisting fracture, a certain level of BMD defined in standard deviation score terms, the T-score (table 4). Many studies have demonstrated that low BMD measured by dual-energy x-ray absorptiometry (DXA) at any skeletal site (spine, hip, or forearm) can predict osteoporotic (fragility) fracture. (See "Clinical manifestations, diagnosis, and evaluation of osteoporosis in postmenopausal women" and "Clinical manifestations, diagnosis, and evaluation of osteoporosis in men" and "Osteoporotic fracture risk assessment", section on 'Fracture prediction'.)

●eGFR ≥30 mL/min/1.73 m² – In patients with chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m², the World Health Organization (WHO) criteria for BMD (T-score 2.5 standard deviations or more below the young adult mean BMD) (table 4) or the presence of a fragility fracture may be used for the diagnosis of osteoporosis, assuming that there are no accompanying biochemical abnormalities (eg, hyperparathyroidism, hyperphosphatemia) that indicate the possible coexistence of renal osteodystrophy or CKD-MBD (mineral bone disorder). (See 'Diagnostic evaluation' below.)

●eGFR <30 mL/min/1.73 m² – In patients with eGFR <30 mL/min/1.73 m², who have low BMD T-scores, or history of fragility fracture, bone physiology is more complex and features of CKD-MBD may predominate. In this setting, a diagnosis of osteoporosis can only be made by excluding CKD-MBD, including renal osteodystrophy. (See 'Diagnostic evaluation' below.)

The diagnosis of bone disease in patients with CKD (particularly with eGFR <30 mL/min/1.73 m²) can be challenging. In the aging population, fragility fractures, reduced glomerular filtration rate (GFR), and low BMD are common. An older patient with CKD and low BMD and/or a fragility fracture may have osteoporosis or another bone and mineral disorder related to CKD (eg, hyperparathyroidism, adynamic bone disease, osteomalacia) [43,44]. Furthermore, osteoporosis frequently coexists with CKD-MBD. There is uncertainty related to the applicability of the established WHO classification of BMD (DXA) according to T-score thresholds (table 4). The WHO thresholds were chosen based upon fracture risk in postmenopausal White women [45]. Similar diagnostic threshold values for men are less well defined, although for any given BMD, the age-adjusted fracture risk is similar in males and females [46].

None of these populations specifically included individuals with CKD. However, the population used to establish the WHO criteria included many older individuals, who also may have had age-related reductions in GFR [45]. The disorders in bone metabolism due to kidney disease are less common with eGFR above 30 mL/min/1.73 m² [2,41,47]. Thus, based upon this evidence in the general population of postmenopausal women and aging men and upon clinical expertise, there has been some agreement that DXA has the same value for patients with eGFR ≥30 mL/min/1.73 m² as it has for patients without CKD [23,26].

In patients with more severe CKD (eGFR <30 mL/min/1.73 m²), the disorders in bone metabolism due to kidney disease are more prevalent and profound, such that the occurrence of a fragility fracture or WHO BMD criteria cannot be used for the diagnosis of osteoporosis [29,43,48]. There are few data to support a specific approach to the diagnosis of osteoporosis in G4 or G5 CKD.

DIAGNOSTIC EVALUATION

Osteoporosis versus CKD-MBD — In patients with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² and low bone mineral density (BMD) (dual-energy x-ray absorptiometry [DXA] T-score ≤-2.5) and/or fragility fracture, the goal of the evaluation is to distinguish osteoporosis from other elements of chronic kidney disease-mineral and bone disorder (CKD-MBD), including renal osteodystrophy (table 1).

The exclusion of renal adynamic bone disease is most important [49-54]. Adynamic bone disease is characterized by low osteoblastic activity and bone formation rates. One may not want to employ pharmacologic agents approved for the treatment of osteoporosis whose mechanism of action is to lower bone turnover when no bone turnover is evident. This concept is most important in light of the data linking low bone turnover to increased vascular calcification in CKD [55]. (See "Adynamic bone disease associated with chronic kidney disease", section on 'Vascular calcification'.)

Laboratory assessment

●eGFR 30 to 60 mL/min/1.73 m² – For patients with eGFR ≥30 but <60 mL/min/1.73 m² with a history of a fragility fracture and/or low BMD (DXA T-score ≤-2.5), we initially measure serum:

•Calcium

•Phosphorus

•Parathyroid hormone (PTH)

•25-hydroxyvitamin D

•Alkaline phosphatase

In those patients with eGFR ≥30 mL/min/1.73 m² who have normal initial biochemical tests, indicating the absence of coexisting CKD-MBD, we make the diagnosis of osteoporosis as in patients without CKD. (See "Clinical manifestations, diagnosis, and evaluation of osteoporosis in postmenopausal women" and "Clinical manifestations, diagnosis, and evaluation of osteoporosis in men".)

In patients with eGFR ≥30 but <60 mL/min/1.73 m² (ie, G3a and G3b) who have abnormalities on initial testing suggestive of CKD-MBD (eg, secondary hyperparathyroidism, hyperphosphatemia), management and monitoring of secondary hyperparathyroidism and mineral metabolism abnormalities, prior to consideration of osteoporosis therapy, is necessary. (See "Management of secondary hyperparathyroidism in adult nondialysis patients with chronic kidney disease" and "Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment", section on 'Defining vitamin D sufficiency' and "Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment", section on 'Vitamin D replacement'.)

●eGFR <30 mL/min/1.73 m² – For patients with an eGFR <30 mL/min/1.73 m² with a history of a fragility fracture and/or low BMD (DXA T-score ≤-2.5), we measure:

•Bone-specific alkaline phosphatase (BSAP)

•Calcium

•Phosphorus

•PTH

•25-hydroxyvitamin D

Measurement of PTH and BSAP may be used to predict underlying bone turnover and can be helpful in excluding the presence of adynamic bone disease [29,56,57]. (See 'Parathyroid hormone' below and 'Bone-specific alkaline phosphatase' below.)

However, bone biopsy is the gold standard for establishing the type of renal bone disease since no combination of biochemical parameters is sufficiently accurate. Indications for bone biopsy are reviewed briefly below and elsewhere. (See 'Bone biopsy' below and "Evaluation of renal osteodystrophy", section on 'Bone biopsy for selected patients'.)

Measurement of 1,25-dihydroxyvitamin D is not recommended, because the values are not stable, the assay is expensive, and the serum does not reflect tissue levels.

Interpretation of lab tests

Calcium, phosphorus, vitamin D — In the majority of patients, serum calcium and phosphorus typically remain normal until glomerular filtration rate (GFR) declines below 25 to 40 mL/min/1.73 m² [58]. In patients with more severe CKD, hypercalcemia may signal the possibility of adynamic bone disease. However, other causes of hypercalcemia (eg, hyperparathyroidism, multiple myeloma) should be considered. The rise in plasma calcium in patients with adynamic bone disease is due, in part, to a marked reduction in the bone uptake of calcium after a calcium load (eg, calcium carbonate to treat hyperphosphatemia). (See "Diagnostic approach to hypercalcemia".)

25-hydroxyvitamin D deficiency is a common finding in predialysis patients with CKD and is associated with elevated PTH levels, which may worsen the manifestations of secondary hyperparathyroidism in this setting (see "Causes of vitamin D deficiency and resistance", section on 'Chronic kidney disease').

Calcitriol (1,25-dihydroxyvitamin D), the most active metabolite of vitamin D, is principally synthesized in the kidney. Circulating calcitriol levels begin to fall when the GFR is less than 40 mL/min/1.73 m² and are typically markedly reduced in patients with end-stage kidney disease [58]. In addition to the loss of functioning renal mass, calcitriol production is also reduced by phosphate retention and elevated levels of fibroblast growth factor 23 (FGF23).

Parathyroid hormone — PTH levels are used as a surrogate to identify the extremes of bone turnover. A serum intact PTH (1-84) that is nine times (eg, 585 pg/mL) or more above the upper limit of the normal range is usually associated with histomorphometric features of osteitis fibrosa cystica, eg, severe parathyroid bone disease [2,49]. Very low PTH levels (<100 pg/mL) are usually associated with adynamic bone disease [2]. If PTH levels are modestly elevated (eg, >150 pg/mL), they are not predictive of underlying bone disease [59,60].

In a cross-sectional study evaluating the ability of serum intact PTH to predict bone turnover in 492 dialysis patients who had bone histomorphometric assessment of bone turnover, a PTH of >323 pg/mL best discriminated high from non-high bone turnover [57]. A PTH level of <103.8 pg/mL best discriminated low from non-low turnover. However, the discriminatory ability of a single level to predict bone turnover was suboptimal (area under the receiver operator curve [AUROC] <0.8) [57]. Nevertheless, in the absence of bone biopsy, PTH levels are the best available parameter to identify the extremes of bone turnover. The ability of serum PTH to predict adynamic bone disease is predicated on the basis that the PTH synthesis is not being blunted by any pharmacologic agent (eg, vitamin D analogues, or cinacalcet).

KDIGO (Kidney Disease Improving Global Outcomes) suggests using PTH trends rather than absolute targets to guide treatment decisions, although this strategy has not been tested specifically for distinguish osteoporosis from other elements of CKD-MBD, including renal osteodystrophy [29,57].

An important consideration in interpreting PTH levels in CKD is not to assume that an elevated PTH in a patient with CKD means that the increased PTH is due only to CKD. It is important to have a broad perspective on other causes of secondary hyperparathyroidism (table 5) such that the finding of an elevated PTH and a reduced eGFR does not automatically imply that the two are linked [61]. Many conditions associated with osteoporosis may have correctable causes of elevated PTH levels even when discovered at the same time as CKD.

Bone-specific alkaline phosphatase — Although biochemical markers of bone turnover cannot be used to diagnose osteoporosis, these markers may provide support that one or another form of renal bone disease may be present, and they are valuable for assessing systemic rates of bone turnover [62-67]. In clinical practice, the marker that has the most value in discriminating bone turnover in CKD is BSAP [56,68]. In particular, a high BSAP may be helpful in excluding the presence of adynamic bone disease. In a cross-sectional study evaluating the ability of serum BSAP to predict bone turnover in 492 dialysis patients who had bone histomorphometric assessment of bone turnover, a BSAP level of <33.1 Unit/L (in an assay with reference range 11.6 to 42.7 Unit/L) best discriminated low from non-low bone turnover (AUROC 0.76) [57]. Thus, in this assay, a serum BSAP above 33.1 Unit/L probably excludes adynamic bone disease. A BSAP of >42.1 Unit/L best discriminated high from non-high bone turnover (AUROC 0.71). The combination of intact PTH and BSAP was slightly better able to discriminate bone turnover than BSAP alone.

The BSAP threshold that best discriminates low bone turnover (adynamic bone disease) will vary with the assay employed. However, a serum BSAP above the upper limit of the laboratory reference range is rarely, if ever, seen in patients with adynamic bone disease unless there has been a recent fracture. Bone cellular activity is reduced in adynamic bone disease, and BSAP is derived from osteoblast activity. While an elevated BSAP provides biochemical evidence that adynamic bone disease is unlikely, the cause of the elevated BSAP requires further evaluation (table 6).

Other markers of bone turnover used in the assessment and management of osteoporosis are not useful in the assessment and management of CKD-MBD. That is because the preferred biochemical marker of bone resorption, serum C-telopeptide (CTX), and the preferred markers of bone formation, monomeric forms of serum propeptide type I collagen (PINP), are both cleared by the kidney [62,64,66,67]. The only available biochemical markers that are not cleared by the kidney are BSAP, tartrate resistant acid phosphatase (TRAP5b, an osteoclast cellular marker), and the trimer form of PINP (table 7) [64,69]. These markers may provide better discriminatory data on turnover than those that are cleared by the kidney and may have value in fracture prediction in pre-dialysis CKD [50,63,64,69].

Bone biopsy — Because it is invasive and requires special equipment and a great deal of expertise, most clinicians do not perform bone biopsies outside clinical research. Bone biopsy should be performed at the discretion of the metabolic bone disease specialist, if an expert skilled in the performance and interpretation of the technique is available. Bone biopsy is particularly important in patients for whom a specific diagnosis of bone disease has significant management implications. In particular, in clinical settings where a management decision (eg, whether to recommend an antiresorptive osteoporosis therapy) must exclude adynamic bone disease and biochemical testing is not helpful in differentiating among the bone disorders, bone biopsy should be performed.

Transiliac bone biopsy is the most reliable test for diagnosing the various forms of renal osteodystrophy (osteomalacia, hyperparathyroid, or adynamic renal bone disease) in patients with CKD [70-72]. Each of these forms of renal bone disease has specific quantitative histomorphometric criteria and management strategies [40,41,50,51]. The presence of renal osteodystrophy suggests more complex physiological abnormalities, and the traditional pharmacologic agents used in osteoporosis may not be effective or safe. (See "Evaluation of renal osteodystrophy" and "Osteoporosis in patients with chronic kidney disease: Management", section on 'Candidates for pharmacologic treatment'.)

There are no established criteria for the diagnosis of osteoporosis by quantitative bone histomorphometry. While osteoporosis, especially the most prevalent form, postmenopausal osteoporosis, has by definition a low bone volume, there may be a range of bone turnover from low to high in the osteoporotic population. Abnormalities in bone microarchitecture or quality may increase fragility even if the bone mass in normal. The absence of an office-based tool for measuring bone quality is a major limitation in the assessment of skeletal health.

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of fragility fracture and/or low bone mineral density (BMD) in patients with chronic kidney disease (CKD) includes the spectrum of mineral and bone disorders of CKD-MBD (mineral and bone disorder). (See "Evaluation of renal osteodystrophy" and "Overview of chronic kidney disease-mineral and bone disorder (CKD-MBD)".)

Patients with kidney disease could also have fractures due to malignancies with metastases, myeloma and marrow diseases, or infections such as tuberculosis.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Osteoporosis".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Osteoporosis (The Basics)" and "Patient education: Chronic kidney disease (The Basics)")

●Beyond the Basics (see "Patient education: Osteoporosis prevention and treatment (Beyond the Basics)" and "Patient education: Chronic kidney disease (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Definitions – Changes in mineral metabolism and bone structure develop early in the course of chronic kidney disease (CKD) and worsen with progressive loss of kidney function. CKD-MBD (mineral and bone disorder) includes abnormalities of calcium, phosphorus, parathyroid hormone (PTH), and/or vitamin D; abnormalities in bone turnover, mineralization, volume, linear growth, or strength; and/or vascular or other soft tissue calcification. (See 'CKD-MBD definition' above.)

●Magnitude of the problem – Both moderate and end-stage CKD are associated with an increased risk of fragility (low trauma) fractures. The exact mechanism for this greater fracture risk in CKD is not clearly established, but there are biological changes in bone metabolism that render the skeleton in patients with progressive CKD (glomerular filtration rate [GFR] stages G3 to G5 (table 2)) more fragile. (See 'Magnitude of the problem' above.)

●Assessment of fracture risk

•FRAX – In clinical practice, a Fracture Risk Assessment Tool (FRAX) may be applied to CKD patients with adjustment of the absolute fracture risk to a higher level in patients with estimated glomerular filtration rate (eGFR) stages G3b to G5 (table 2). (See 'Fracture risk assessment tool' above.)

•Bone mineral density: DXA

-CKD and eGFR ≥30 mL/min/1.73 m² – For patients with CKD, eGFR ≥30 mL/min/1.73 m², and risk factors for fracture, bone mineral density (BMD) (dual-energy x-ray absorptiometry [DXA]) testing may be used to assess fracture risk.

-eGFR <30 mL/min/1.73 m² – Although BMD testing is not routinely performed to assess fracture risk in patients with CKD and eGFR <30 mL/min/1.73 m², it may be obtained in selected patients with eGFR <30 mL/min/1.73 m² who have fragility fracture and no evidence of CKD-MBD, including renal osteodystrophy, particularly when osteoporosis therapy is being considered. (See 'Bone mineral density: DXA' above.)

●Diagnosis of osteoporosis in CKD – It is difficult to diagnose osteoporosis in the setting of CKD-MBD. Patients with CKD may have osteoporosis either before or after developing kidney disease. Osteoporosis, a term that includes major alterations in bone quality, is probably a universal feature accompanying bone disease in all forms of renal bone disease (table 1).

•eGFR ≥30 mL/min/1.73 m² – In patients with CKD and eGFR ≥30 mL/min/1.73 m², we use the World Health Organization (WHO) criteria (BMD T-score 2.5 standard deviations or more below the young adult mean BMD) or the presence of a fragility fracture to make the diagnosis of osteoporosis, assuming that there are no accompanying biochemical abnormalities (hyperparathyroidism, hyperphosphatemia) that indicate the coexistence of renal osteodystrophy or CKD-MBD (table 4).

•eGFR <30 mL/min/1.73 m² – In patients with eGFR <30 mL/min/1.73 m², who have low BMD T-scores or history of fragility fracture, bone physiology is more complex, and features of CKD-MBD may predominate. In this setting, a diagnosis of osteoporosis can only be made by excluding CKD-MBD, including renal osteodystrophy, with laboratory tests and sometimes a bone biopsy (table 1). (See 'Diagnosis' above.)

●Diagnostic evaluation

•Laboratory assessment – For patients with eGFR ≥30 but <60 mL/min/1.73 m² and a history of a fragility fracture and/or low BMD (DXA T-score ≤-2.5), we initially measure serum calcium, phosphorus, PTH, 25-hydroxyvitamin D, and alkaline phosphatase. (See 'Diagnostic evaluation' above.)

For similar patients with eGFR <30 mL/min/1.73 m², we also measure bone specific alkaline phosphatase (BSAP). Along with PTH, BSAP may have value in differentiating among the various forms of renal osteodystrophy. (See 'Diagnostic evaluation' above.)

•Role of bone biopsy – Because it is invasive and requires special equipment and a great deal of expertise, most clinicians do not perform bone biopsies outside clinical research. Bone biopsy should be performed at the discretion of the metabolic bone disease specialist, if an expert skilled in the performance and interpretation of the technique is available. Bone biopsy is particularly important in patients for whom a specific diagnosis of bone disease has significant management implications. (See 'Bone biopsy' above.)