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Keywords:

  • absorptiometry;
  • bone;
  • bone density;
  • fractures;
  • osteoporosis;
  • photon

SUMMARY

  1. Top of page
  2. SUMMARY
  3. TECHNIQUES FOR MEASURING BONE DENSITY
  4. PREDICTING FRACTURE RISK IN THE GENERAL POPULATION
  5. BONE DENSITY IN EARLY STAGES OF CKD
  6. BONE DENSITY MEASUREMENTS IN PATIENTS RECEIVING HAEMODIALYSIS
  7. CROSS-SECTIONAL STUDIES RELATING BMD TO FRACTURES
  8. BMD AND RELATIONSHIP TO BONE VOLUME
  9. BMD AND DIFFERENT TYPES OF RENAL OSTEODYSTROPHY
  10. BMD CHANGE IN INDIVIDUALS
  11. BMD AND PREDICTION OF RESPONSE TO OSTEOPOROSIS THERAPY
  12. SUMMARY
  13. ACKNOWLEDGEMENT
  14. REFERENCES

Skeletal fractures are common in dialysis patients. Bone density measurements predict fractures in the general population, but in patients with chronic kidney disease (CKD) there is limited ability to predict fractures with these techniques. A review of the literature in patients with CKD stage 5 shows that bone density in the cortical bone of the radius or hip is generally lower compared with normal reference ranges by about one to two standard deviations, whereas in the spine bone density tends to be closer to the average expected values. The bone density is not able to predict the underlying histology in patients with renal osteodystrophy. The serum PTH levels are inversely related to bone density in some studies, and not related in other studies, but none found a positive association of serum parathyroid hormone (PTH) and bone density. There are very few data about longitudinal changes of bone density in these patients, and also inadequate studies of whether osteoporosis medications are effective in this population. Therefore, at this time the clinical utility of bone density measurements in patients with CKD-5 is uncertain.

Skeletal fractures have been recognized as one of the most troublesome complications of long-term haemodialysis since the 1966 report of the first 22 patients who received this treatment.1 Fractures occurred in 47% of the patients. Since then, several studies of fracture prevalence and incidence have been reported (see Table 1).1–19 The prevalence ranges from 10% to 40% in dialysis populations. About half of patients older than 50 years have had a fracture. The age-adjusted incidence rate of hip fractures in all patients who started dialysis in the US from 1989 to 1996 was 4.4 times greater than those in the general population.7 The ratio of observed fractures in the dialysis population to the fracture incidence in the normal population varied with age; from about 90:1 in those younger than 45, about 22:1 in those between 45 and 54, and about 2:1 in those older than 85. The absolute number of fractures was greater in elderly patients, in women, and in those with longer exposure to dialysis.

Table 1.  Prevalence and incidence of skeletal fractures in patients with CKD-5D
AuthorYearsnPatientsPrevalenceIncidence (%/year)
Any (%)Hip (%)Spine (%)AnyHip
  1. CKD, chronic kidney disease; HD, haemodialysis; PD, peritoneal dialysis; USRDS, United States Renal Dialysis.

Pendras6619First HD patients 47   
Rubini6929HD27    
Parfitt7216HD44 25  
Yamaguchi96124HD10 11  
Atsumi99187HD  21  
Gerakis0062HD11    
Alem00182 493Males    0.74
Alem00143 971Females    1.36
Coco001 272HD    1.39
Stehman-Breen004 952HD    0.69
Ball02101 039USRDS   0.29 
Jamal02104HD > 55 years52 33  
Kaji02183HD 7.6   
Urena0370HD30 7  
Block0440 538HD   0.52 
Inaba05114PD > 65 years  18  
Danese069 007USRDS    0.65
Elder06242Pre-Tx  28  
Ersoy06292PD10    
Jadoul0612 782HD, DOPPS 2.6 2.560.89
Jamal0652HD > 50 years52    
Kaneko067 159USRDS    1.01
Mitterbauer071 777HD   4.1 

Fractures occur when a mechanical force overwhelms the bone strength. Over the last 25 years many studies have sought to identify the factors that contribute to bone strength, including the size and shape of the bone, porosity, micro-architecture and material properties of the bone tissue. The same mechanical principles that pertain to buildings and bridges apply to the skeleton.

Bone mineral density (BMD) measurements using dual energy x-ray absorptiometry (DXA) measure only one aspect of bone strength and the goal of treating a patient is to prevent fractures, not merely to improve a bone density measurement. This is particularly true in chronic kidney disease (CKD), because factors in addition to bone density play a large role in determining the strength of the bone and the risk of a fracture.

TECHNIQUES FOR MEASURING BONE DENSITY

  1. Top of page
  2. SUMMARY
  3. TECHNIQUES FOR MEASURING BONE DENSITY
  4. PREDICTING FRACTURE RISK IN THE GENERAL POPULATION
  5. BONE DENSITY IN EARLY STAGES OF CKD
  6. BONE DENSITY MEASUREMENTS IN PATIENTS RECEIVING HAEMODIALYSIS
  7. CROSS-SECTIONAL STUDIES RELATING BMD TO FRACTURES
  8. BMD AND RELATIONSHIP TO BONE VOLUME
  9. BMD AND DIFFERENT TYPES OF RENAL OSTEODYSTROPHY
  10. BMD CHANGE IN INDIVIDUALS
  11. BMD AND PREDICTION OF RESPONSE TO OSTEOPOROSIS THERAPY
  12. SUMMARY
  13. ACKNOWLEDGEMENT
  14. REFERENCES

Most recent studies have used DXA. Standard skeletal sites are the lumbar spine, the proximal femur and, less commonly, the total body. This technique utilizes attenuation of radiation by bones or soft tissues. Anything within the radiation path can elevate the measurements, such as soft tissue calcification, peritoneal fluid, calcium tablets in the intestine or external artifacts. The software detects the edges of the bones whenever continguous pixels exceed a set threshold density. This can be a source of error when the bone density is low or the edge is irregular, especially when there is a large surface compared with volume (as in measuring individual vertebrae instead of a block of four adjacent vertebrae). The resulting values are presented as BMD. These values do not represent the volumetric density (g/cm3), but rather an areal density representing the grams of bone mineral in a projected area of bone, that is, the bone mineral content divided by the bone area and measured as g/cm2. As a consequence, the values will depend on the orientation of the bone; if the radiation passes through a long axis, the result will be higher than if it passes through a short axis. This means that positioning in a standard rotation is essential. Patients with scoliosis have inaccurate measurements because the projected area is not the usual shape nor has the usual contribution of posterior elements. The bone density measured at the proximal femur can change significantly with minor rotation of the hip joint. Another consequence of the two-dimensional measurement is that smaller bones have lower areal BMD than larger bones, even if the true density per cubic centimetre of bone is the same. This is because the volume of growing bones increases at a faster rate than the cross-sectional area and is particularly important when interpreting BMD in children who are smaller than other children of the same age.20

Because the instrument will measure everything within a beam of radiation, it is impossible to measure the interior trabecular bone without including the cortex. However, certain sites contain greater percentages of trabecular bone (by weight). The vertebral body is 42% trabecular,21 the proximal femur about 25% trabecular, the total body about 80% cortical and the midradius about 90% cortical bone, while the distal radius contains a mixture of trabecular and cortical bone. These distinctions are important because bone remodeling in patients with renal osteodystrophy is different in trabecular bone than in cortical bone.

Quantitated computed tomography (QCT) has been used in some studies of bone density. This technique has the advantage of measuring the bone in three dimensions and the results are volumetric (g/cm3). Disadvantages are higher radiation dose and cost. Exact positioning is essential for good precision; it is difficult to reproduce the angle of a slice taken through a vertebral body. The distal radius can be measured with greater precision and resolution. A problem with QCT is that the measurement includes marrow (red and yellow); if the proportions of these change, that change will materially change the value derived, even if there is no change in the actual bone component. An advantage of QCT is that it can clearly separate the trabecular from the cortical bone.22 QCT measurements should include a phantom for calibration.

Neither QCT nor DXA has enough resolution to measure the porosity of bone and they cannot distinguish between a porous bone with dense material and a less porous bone which is not fully mineralized. An emerging technique is high-resolution magnetic resonance imaging, which can create a ‘virtual biopsy’ of the bone, with enough resolution to follow changes in individual trabeculae over time.23

Other techniques include ultrasound attenuation of the calcaneous and radiographic densitometry of peripheral bones. They do not have the same extensive reference database as DXA, and because there are only a few reports of these in dialysis patients they are not further considered here.

PREDICTING FRACTURE RISK IN THE GENERAL POPULATION

  1. Top of page
  2. SUMMARY
  3. TECHNIQUES FOR MEASURING BONE DENSITY
  4. PREDICTING FRACTURE RISK IN THE GENERAL POPULATION
  5. BONE DENSITY IN EARLY STAGES OF CKD
  6. BONE DENSITY MEASUREMENTS IN PATIENTS RECEIVING HAEMODIALYSIS
  7. CROSS-SECTIONAL STUDIES RELATING BMD TO FRACTURES
  8. BMD AND RELATIONSHIP TO BONE VOLUME
  9. BMD AND DIFFERENT TYPES OF RENAL OSTEODYSTROPHY
  10. BMD CHANGE IN INDIVIDUALS
  11. BMD AND PREDICTION OF RESPONSE TO OSTEOPOROSIS THERAPY
  12. SUMMARY
  13. ACKNOWLEDGEMENT
  14. REFERENCES

A meta-analysis performed by the World Health Organization found that BMD, age, race and gender strongly predicted fractures.24 They recently developed a method of assessing fracture risk that also includes weight, previous adult fracture, parental history of hip fracture, cigarette smoking, alcohol use, rheumatoid arthritis and glucocorticoid use.25 The equations used to calculate the risk score were derived from international prospective studies of 46 340 persons followed for 4 years and were validated in 230 486 persons followed for 5 years, with a mean age of 63 years. The risk of a hip fracture was 4.2 times higher for every standard deviation increase in the risk score.26 The large epidemiological studies did not enroll enough persons with CKD stage 5 to allow prediction of fracture risk.

BONE DENSITY IN EARLY STAGES OF CKD

  1. Top of page
  2. SUMMARY
  3. TECHNIQUES FOR MEASURING BONE DENSITY
  4. PREDICTING FRACTURE RISK IN THE GENERAL POPULATION
  5. BONE DENSITY IN EARLY STAGES OF CKD
  6. BONE DENSITY MEASUREMENTS IN PATIENTS RECEIVING HAEMODIALYSIS
  7. CROSS-SECTIONAL STUDIES RELATING BMD TO FRACTURES
  8. BMD AND RELATIONSHIP TO BONE VOLUME
  9. BMD AND DIFFERENT TYPES OF RENAL OSTEODYSTROPHY
  10. BMD CHANGE IN INDIVIDUALS
  11. BMD AND PREDICTION OF RESPONSE TO OSTEOPOROSIS THERAPY
  12. SUMMARY
  13. ACKNOWLEDGEMENT
  14. REFERENCES

The NHANES population-based study measured hip BMD by DXA and serum creatinine in 13 831 people. Based on the Cockcroft-Gault equation, 18% of adult women with stage 3 CKD and 53% of women with stage 4 CKD had osteoporosis.27 Osteoporosis was less common in men with CKD. The percentage of people with low bone density was much greater in those with CKD than in those with normal kidney function, but many persons with CKD are older and have less muscle mass, so that the correlation between BMD and CKD was not significant when adjusted for sex, age and weight.28

Early stages of CKD are common in elderly persons who have low bone density. In the US population, 84% of women with osteoporosis had CKD stage 3 to 4. However, in osteoporotic women younger than 60 the prevalence of CKD stage 4 was very low.

BONE DENSITY MEASUREMENTS IN PATIENTS RECEIVING HAEMODIALYSIS

  1. Top of page
  2. SUMMARY
  3. TECHNIQUES FOR MEASURING BONE DENSITY
  4. PREDICTING FRACTURE RISK IN THE GENERAL POPULATION
  5. BONE DENSITY IN EARLY STAGES OF CKD
  6. BONE DENSITY MEASUREMENTS IN PATIENTS RECEIVING HAEMODIALYSIS
  7. CROSS-SECTIONAL STUDIES RELATING BMD TO FRACTURES
  8. BMD AND RELATIONSHIP TO BONE VOLUME
  9. BMD AND DIFFERENT TYPES OF RENAL OSTEODYSTROPHY
  10. BMD CHANGE IN INDIVIDUALS
  11. BMD AND PREDICTION OF RESPONSE TO OSTEOPOROSIS THERAPY
  12. SUMMARY
  13. ACKNOWLEDGEMENT
  14. REFERENCES

Figure 1 shows the average values of BMD in studies of patients with CKD Stage 5D.4–6,12,13,16,29–76 These values are expressed as Z-scores, which compare BMD in the patients with the BMD from the reference values of age- and gender-matched persons in the community. The prevalence of low BMD is influenced by the age of the cohort, the number of men, the proportion of non-Caucasians, the average duration of dialysis and the skeletal sites used to define osteoporosis. Most of the studies found that spine BMD was relatively higher than BMD at the hip or radius.

image

Figure 1. The graph is a summary of studies of bone density measured at the radius, spine and hip in patients with CKD stage 5. Bone density is presented as the Z-score, which is the number of standard deviations from normal persons of the same age and gender. Within each group the points are arranged left to right in chronological order; each point is the mean value for a study. Squares are used for combined data and if data from men and women were reported separately, points for the women are circles and for men are diamonds. Size of points is larger in studies with greater numbers of subjects. Data from studies that reported g/cm2 were converted to Z-scores (hip and forearm) using the average age of the group of subjects and published normal reference ranges. CKD, chronic kidney disease.

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CROSS-SECTIONAL STUDIES RELATING BMD TO FRACTURES

  1. Top of page
  2. SUMMARY
  3. TECHNIQUES FOR MEASURING BONE DENSITY
  4. PREDICTING FRACTURE RISK IN THE GENERAL POPULATION
  5. BONE DENSITY IN EARLY STAGES OF CKD
  6. BONE DENSITY MEASUREMENTS IN PATIENTS RECEIVING HAEMODIALYSIS
  7. CROSS-SECTIONAL STUDIES RELATING BMD TO FRACTURES
  8. BMD AND RELATIONSHIP TO BONE VOLUME
  9. BMD AND DIFFERENT TYPES OF RENAL OSTEODYSTROPHY
  10. BMD CHANGE IN INDIVIDUALS
  11. BMD AND PREDICTION OF RESPONSE TO OSTEOPOROSIS THERAPY
  12. SUMMARY
  13. ACKNOWLEDGEMENT
  14. REFERENCES

For patients with CKD-5D, no prospective studies have been published that measured bone density and followed patients to determine the subsequent risk of a fracture. A literature review yielded 14 cross-sectional studies which reported BMD in dialysis patients with or without fractures (shown in Table 2).4–6,11–13,15,16,18,30,77–80 The results of these studies are mixed, and predominantly do not show any differences in BMD at the hip or spine between patients with or without fractures. However, BMD at the wrist or total body was frequently lower in those with fractures.

Table 2.  Relationship between BMD and fracture prevalence in patients with CKD-5
AuthorYearsn% malePatientsN FxFractureSkeletal site of BMD measurement
SpineHipWristBody
  1. †Adjusted for age. BMD, bone mineral density; CKD, chronic kidney disease; HD, haemodialysis; No, BMD in patients with fracture are not significantly different from those without fracture; nr, BMD was measured but results was not reported; PD, peritoneal dialysis; Pre-Tx, prior to kidney transplantation.

Yamaguchi9612447HD27Clin & VertNo Yes 
Atsumi99187100HD39VertebralYes  Yes
Gerakis006266HD7ClinicalNoNo  
Fontaine008858HD11Clin & VertYesYesYes 
Jamal0210471HD > 55 years54Clin & VertNoNo  
Kaji0218355HD14HipNo Yes 
Urena037060HD21Clin & VertNoNoNoYes
Negri046531PD6ClinicalNoNo  
Inaba051140PD > 65 years21VertebralNo No 
Elder0624261Pre-Tx89Clin & VertNoYesnr 
Ersoy0629256PD24ClinicalNoNo  
Jamal065271HD > 50 years27Clin & VertNoNoYes 
Dolgos0813370Pre-Tx38Clinicalnrnr Yes
Mares097356HD15VertebralNo   

A meta-analysis by Jamal et al.81 included six of these studies and found no increased risk of hip fracture related to BMD at the hip. The slight difference in BMD at the spine was barely significant. At the distal radius, BMD values were significantly lower in patients who had a fracture than in those who did not. In a study of 187 men, Atsumi et al.5 found that each standard deviation lowering of spine bone density increased the odds ratio of a spine fracture by 2.0. Elder et al.30 studied 242 patients and found lower BMD at the hip in cases with fragility fractures and a trend towards a lower spine BMD. Ersoy et al.16 studied 292 patients receiving peritoneal dialysis and found no relationship between hip or spine BMD and fractures.

One could argue that these studies in CKD patients are not as large as those in the general population, but early studies in osteoporosis patients were small and cross-sectional and they provide an interesting comparison. A review of 41 such studies between 1981 and 1992 concluded that the relationship between bone mass and bone failure was strong. Almost all of these studies found significantly lower BMD in the hip or spine in those patients who had fractures.82

There are several potential reasons for the poor performance of DXA in patients with CKD-5. Vertebral measurements may overestimate BMD because of arthritic conditions, scoliosis and aortic calcifications. CKD patients have poor bone quality that cannot be measured by absorptiometry. Abnormal micro-architecture, mineralization density, crystal deposition in the bone matrix or abnormalities in the matrix itself could all contribute to loss of bone strength. Patients with CKD, especially those with high serum parathyroid hormone (PTH), have increased cancellous bone volume but decreased cortical thickness,41 which can alter the relationship between the overall bone strength and the BMD findings. Furthermore, patients with CKD may experience more trauma to the skeleton if they have more frequent falls. A study of fall prevalence in osteoporotic patients showed a greater risk in those with estimated glomerular filtration rate (eGFR) less than 65 mL/min, especially when they were taking glucocorticoids.83 Patient with CKD may have more postural hypotension, weaker muscles and problems with balance or peripheral neuropathy, all of which increase risk of falling.

BMD AND RELATIONSHIP TO BONE VOLUME

  1. Top of page
  2. SUMMARY
  3. TECHNIQUES FOR MEASURING BONE DENSITY
  4. PREDICTING FRACTURE RISK IN THE GENERAL POPULATION
  5. BONE DENSITY IN EARLY STAGES OF CKD
  6. BONE DENSITY MEASUREMENTS IN PATIENTS RECEIVING HAEMODIALYSIS
  7. CROSS-SECTIONAL STUDIES RELATING BMD TO FRACTURES
  8. BMD AND RELATIONSHIP TO BONE VOLUME
  9. BMD AND DIFFERENT TYPES OF RENAL OSTEODYSTROPHY
  10. BMD CHANGE IN INDIVIDUALS
  11. BMD AND PREDICTION OF RESPONSE TO OSTEOPOROSIS THERAPY
  12. SUMMARY
  13. ACKNOWLEDGEMENT
  14. REFERENCES

The relationship between BMD and bone volume determined by biopsy is not well defined. In patients with postmenopausal osteoporosis there is a significant but weak correlation between bone volume on biopsy and BMD measured by DXA. The studies in dialysis patients have all measured cancellous bone volume. In patients with CKD, Lindergard et al.41 measured bone volume/tissue volume (BV/TV) on 71 biopsies from dialysis patients, and did not see a correlation with BMD at the radius. Similar results were seen by Gerakis et al.6 in a study of 62 patients. On the other hand, Torres et al.84 found a correlation coefficient of 0.82 between BV/TV and QCT of the spine and Van Eps et al.85 found lower DXA values in patients with low bone volume on biopsy. Cancellous bone volume measurements are more likely to be related to bone density measured at skeletal locations such as the spine, which contains predominantly cancellous bone.

BMD AND DIFFERENT TYPES OF RENAL OSTEODYSTROPHY

  1. Top of page
  2. SUMMARY
  3. TECHNIQUES FOR MEASURING BONE DENSITY
  4. PREDICTING FRACTURE RISK IN THE GENERAL POPULATION
  5. BONE DENSITY IN EARLY STAGES OF CKD
  6. BONE DENSITY MEASUREMENTS IN PATIENTS RECEIVING HAEMODIALYSIS
  7. CROSS-SECTIONAL STUDIES RELATING BMD TO FRACTURES
  8. BMD AND RELATIONSHIP TO BONE VOLUME
  9. BMD AND DIFFERENT TYPES OF RENAL OSTEODYSTROPHY
  10. BMD CHANGE IN INDIVIDUALS
  11. BMD AND PREDICTION OF RESPONSE TO OSTEOPOROSIS THERAPY
  12. SUMMARY
  13. ACKNOWLEDGEMENT
  14. REFERENCES

There are some inconsistent reports about relationship between BMD and type of renal osteodystrophy. Five small studies found similar DXA results in all the types29,86–88 and one found a difference using spine QCT,89 which was 5% above the normal mean in patients with high bone turnover and 30% below the mean in those with low turnover. In a larger study, Gerakis et al.6 found that BMD by DXA was lower in osteitis fibrosa (OF) than in adynamic bone, but there were wide ranges in both types. Fletcher et al.90 also found lower DXA results in patients with severe OF, particularly at the proximal forearm. The patients with adynamic disease also had a low forearm BMD. At the spine, those with mixed lesions were 2.85 standard deviations higher than normal, compared with −0.77 SD lower in those with severe OF.

Table 3 shows results from studies that measured BMD as well as serum PTH. None of these studies found a positive relationship between PTH and BMD; either the relationship was not significant or there was a significant inverse correlation.5,6,13,16,18,30,62,63,67,76,91–95

Table 3.  Relationship of BMD to PTH in patients with CKD-5D
AuthorYearsnRelationship of BMD to PTH
  1. BMD, bone mineral density; CKD, chronic kidney disease; PTH, parathyroid hormone.

Taal9988Inverse
Atsumi99187Inverse (body, not spine)
Gerakis0062Inverse
Kokado00293Inverse
Barnas0190Not related
Pecovnik0250Inverse
Ueda02195Inverse to change in BMD
Urena0370Inverse
Nakashima0383Inverse
Negri0465Inverse (body, not spine or hip)
Nakashima06201Inverse to change in BMD
Jamal0652Inverse
Wittersheim0679Inverse
Ersoy06292Not related
Elder06242Inverse
Sit0770Not related
Doumouchtis0854Not related

BMD CHANGE IN INDIVIDUALS

  1. Top of page
  2. SUMMARY
  3. TECHNIQUES FOR MEASURING BONE DENSITY
  4. PREDICTING FRACTURE RISK IN THE GENERAL POPULATION
  5. BONE DENSITY IN EARLY STAGES OF CKD
  6. BONE DENSITY MEASUREMENTS IN PATIENTS RECEIVING HAEMODIALYSIS
  7. CROSS-SECTIONAL STUDIES RELATING BMD TO FRACTURES
  8. BMD AND RELATIONSHIP TO BONE VOLUME
  9. BMD AND DIFFERENT TYPES OF RENAL OSTEODYSTROPHY
  10. BMD CHANGE IN INDIVIDUALS
  11. BMD AND PREDICTION OF RESPONSE TO OSTEOPOROSIS THERAPY
  12. SUMMARY
  13. ACKNOWLEDGEMENT
  14. REFERENCES

With DXA, the measurement error may exceed the magnitude of clinically important bone loss or gain. A walk around the room causes the measurement to change on average 1.7% with standard deviation 1.3%, range from 0 to 7.4%, and the coefficient of variation is 1.52%. A change greater than 4% was seen in 7% of the women. This compares to a usual bone loss of about 1% per year (our unpublished observations from 300 repeat measurements). Precision can be calculated by various methods,96 but may underestimate the error seen in clinical practice when scans are performed on different dates.97 Thus, for individual patients, clinically important changes in bone mass may take several years to detect. Only severe loss can be reliably measured with two determinations.

BMD AND PREDICTION OF RESPONSE TO OSTEOPOROSIS THERAPY

  1. Top of page
  2. SUMMARY
  3. TECHNIQUES FOR MEASURING BONE DENSITY
  4. PREDICTING FRACTURE RISK IN THE GENERAL POPULATION
  5. BONE DENSITY IN EARLY STAGES OF CKD
  6. BONE DENSITY MEASUREMENTS IN PATIENTS RECEIVING HAEMODIALYSIS
  7. CROSS-SECTIONAL STUDIES RELATING BMD TO FRACTURES
  8. BMD AND RELATIONSHIP TO BONE VOLUME
  9. BMD AND DIFFERENT TYPES OF RENAL OSTEODYSTROPHY
  10. BMD CHANGE IN INDIVIDUALS
  11. BMD AND PREDICTION OF RESPONSE TO OSTEOPOROSIS THERAPY
  12. SUMMARY
  13. ACKNOWLEDGEMENT
  14. REFERENCES

Randomized placebo-controlled trials of osteoporosis medications in the general population have shown reduction of fracture rates. Although some investigators have found a relationship between the degree of increase in bone density and the reduction in fractures, this is debated.98 The most striking counter-example is fluoride, which increased spine bone density steadily by 35% over 4 years. The fracture rates, however, were worse in those taking fluoride.99

We analysed data from the alendronate Fracture Intervention Trial and found that the 1-year change in the bone alkaline phosphatase was significantly related to reduction of all kinds of fractures, whereas the 1-year change in spine BMD was not associated with the risk of fracture; and change in hip BMD was associated only with spine fractures but not hip or non-spine fractures.100 The increased bone density is mostly due to increased mineralization of bone material that was already present, which is currently considered to contribute to bone strength.101 The major reason bone strength is better in patients treated with the medications, as compared with placebo, is that the reduction in turnover will reduce the risk of trabecular plate perforations. A study of raloxifene found that the the percent change in osteocalcin was better able to predict the reduction in vertebral fracture risk than the percent change in femoral neck BMD.102

Further evidence for the importance of reducing bone turnover was found in an analysis of the fracture reduction in patients according to their bone turnover at the initiation of alendronate. Those in the lowest tertile of bone formation as assessed by Procollagen Type 1 N-terminal extension peptide (P1NP) did not have any reduction in fractures, whereas those in the highest tertile had enough fracture reduction to make the effect significant for the entire group.103 This has implications for bisphosphonate efficacy in dialysis patients, because a large percentage of them already have adynamic bone disease.

In dialysis patients, there are very limited data about the effect of medications for osteoporosis. Small studies have shown that bisphosphonates increase the bone density, but these studies have enrolled small numbers of patients for short durations, which provides insufficient power to assess the fracture rates.75,104 Many of the patients with CKD-5D have low bone turnover, and thus even an increase of bone density may not improve the risk of fracture.

Increases in bone density, therefore, do not always mean the bone strength is improved, because there may be concomitant worsening of the bone quality. On the other hand, it is difficult to imagine that a loss of bone density could be beneficial, except in rare cases of osteosclerosis. When medications or therapy are shown to cause loss of bone density, physicians should be concerned. Within the dialysis population, it is possible that treatment for disorders of mineral metabolism could cause a negative calcium balance which would harm the skeleton. There are no adequate clinical trials that have included longitudinal measurements of bone density. Prospective studies of factors which are related to bone loss are needed in these patients.

SUMMARY

  1. Top of page
  2. SUMMARY
  3. TECHNIQUES FOR MEASURING BONE DENSITY
  4. PREDICTING FRACTURE RISK IN THE GENERAL POPULATION
  5. BONE DENSITY IN EARLY STAGES OF CKD
  6. BONE DENSITY MEASUREMENTS IN PATIENTS RECEIVING HAEMODIALYSIS
  7. CROSS-SECTIONAL STUDIES RELATING BMD TO FRACTURES
  8. BMD AND RELATIONSHIP TO BONE VOLUME
  9. BMD AND DIFFERENT TYPES OF RENAL OSTEODYSTROPHY
  10. BMD CHANGE IN INDIVIDUALS
  11. BMD AND PREDICTION OF RESPONSE TO OSTEOPOROSIS THERAPY
  12. SUMMARY
  13. ACKNOWLEDGEMENT
  14. REFERENCES

Patients with CKD stage 5 have renal osteodystrophy with associated abnormalities in mineral metabolism, and BMD measured by DXA is not as closely associated with fracture as in the general population. BMD is generally low in cortical areas, such as the radius, and measurements at the hip are usually lower than at the spine. The pathophysiology of renal osteodystrophy is not the same as age-related osteoporosis. Therefore the therapies that improve fracture risk in postmenopausal osteoporosis may not be beneficial in patients with renal osteodystrophy. Intuitively, it seems that a decreasing BMD or a very low BMD should increase the risk of fractures, but this has not been documented by prospective studies. Anabolic agents which safely increase the bone volume are needed, but they are not available. Hopefully future research will both clarify the relationship between BMD and bone strength in this population and develop medications that can effectively increase the bone strength and reduce the fracture rates.

REFERENCES

  1. Top of page
  2. SUMMARY
  3. TECHNIQUES FOR MEASURING BONE DENSITY
  4. PREDICTING FRACTURE RISK IN THE GENERAL POPULATION
  5. BONE DENSITY IN EARLY STAGES OF CKD
  6. BONE DENSITY MEASUREMENTS IN PATIENTS RECEIVING HAEMODIALYSIS
  7. CROSS-SECTIONAL STUDIES RELATING BMD TO FRACTURES
  8. BMD AND RELATIONSHIP TO BONE VOLUME
  9. BMD AND DIFFERENT TYPES OF RENAL OSTEODYSTROPHY
  10. BMD CHANGE IN INDIVIDUALS
  11. BMD AND PREDICTION OF RESPONSE TO OSTEOPOROSIS THERAPY
  12. SUMMARY
  13. ACKNOWLEDGEMENT
  14. REFERENCES