Frequency of Bone Mineral Density Testing in Adult Kidney Transplant Recipients from Ontario,Canada: A Population-Based Cohort Study

Abstract

French

Background:

We lack consensus on the clinical value, frequency, and timing of bone mineral density (BMD) testing in kidney transplant recipients. This study sought to determine practice patterns in BMD testing across kidney transplant centres in Ontario, Canada, and to compare the frequency of testing in kidney transplant recipients to non-transplant reference groups.

Methods:

Using healthcare databases from Ontario, Canada we conducted a population-based cohort study of adult kidney transplant recipients who received a transplant from 1994-2009. We used logistic regression to determine if there was a statistically significant difference across transplant centres in the decision to perform at least one BMD test after transplantation, adjusting for covariates that may influence a physician's decision to order a BMD test. We used the McNemar's test to compare the number of recipients who had at least one BMD test to non-transplant reference groups (matching on age, sex, and date of cohort entry).

Results:

In the first 3 years after transplant, 4821 kidney transplant recipients underwent 4802 BMD tests (median 1 test per recipient, range 0 to 6 tests), costing $600,000 (2014 CAD equivalent dollars). Across the six centres, the proportion of recipients receiving at least one BMD test varied widely (ranging from 15.6 to 92.1 %; P < 0.001). Over half (58 %) of the recipients received at least one BMD test post-transplant, a value higher than two non-transplant reference groups (general population with a previous non-vertebral fracture [hip, forearm, proximal humerus], 13.8 %; general population with no previous non-vertebral fracture, 8.5 %; P value <0.001 for each of the comparisons).

Conclusions:

There is substantial practice variability in BMD testing after transplant. New high-quality information is needed to inform the utility, optimal timing, and frequency of BMD testing in kidney transplant recipients.

Keywords

Bone mineral density Kidney transplant recipient Bone

What was known before

Kidney transplant recipients have a higher risk of fracture compared to the healthy general population. However, the best way to identify recipients at high risk is unknown. Bone mineral density (BMD) is widely used in the general population to help identify patients with a high fracture risk, but its utility in the kidney transplant population is unclear. Limited evidence can lead to substantial practice variability. However, practice patterns for BMD testing in kidney transplant recipients from Ontario, Canada, are unknown.

What this adds

Despite limited evidence on the utility of BMD testing, many kidney transplant recipients receive a test in the 3 years after transplant, and significant practice variability in BMD testing was observed across transplant centres. These results indicate future studies are needed to better understand the utility, frequency, timing, and cost-effectiveness of BMD testing in kidney transplant recipients.

Background

It is well accepted that kidney transplant recipients have a higher risk of fracture compared to the healthy general population [1 –4]. For example, Ramsey-Goldman et al., found female kidney transplant recipients aged 25–44 years had an 18 times higher fracture risk compared to individuals from the general population of similar age and sex [1]; however, recent observations suggest that the absolute incidence is low with only 1.7 % of recipients sustaining a hip fracture in the 10-years after transplantation (high risk defined as a 10-year risk >3 %) [4 –7]. The reasons for this higher risk are multifactorial and include pre-existing chronic kidney disease-mineral and bone disorder (CKD-MBD) and glucocorticoid administration after transplantation [8]. In the general population, Osteoporosis Canada guidelines recommend bone mineral density (BMD) testing is done in individuals at a high risk of fracture, as a decreased BMD can help risk stratify those individuals at higher risk of fracture [9 –11]. However, in the kidney transplant population, the ability of BMD to predict fracture is unclear [12 –14]. Limited evidence can lead to substantial practice variability. Therefore, we conducted a population-based study to determine the frequency, total cost, and the variability in BMD testing across all six transplant centres in Ontario, Canada. To help put the frequency of BMD testing into context, we also compared the frequency of testing in transplant recipients to non-transplant reference groups (matching on age, sex, and date of cohort entry).

Methods

Design and setting

We used linked healthcare databases from the province of Ontario, Canada to conduct this study. Universal access to physician and hospital services is provided to all Ontario residents. These datasets were linked using unique encoded identifiers and analyzed at the Institute for Clinical Evaluative Sciences (ICES). This study was approved by the institutional review board at Sunnybrook Health Sciences Centre, Toronto, Canada.

Data sources

Information on Ontario kidney transplant recipients is provided by the Canadian Organ Replacement Register. Information on Ontario physicians' billing claims for inpatient and outpatient services is reported by the Ontario Health Insurance Plan (OHIP). The Ontario Registered Persons Database provides information on demographics and vital status. Prescription drug utilization data is provided from the Ontario Drug Benefit Plan, which is a universal drug plan for individuals ≥65 years. It also provides information since April 1997 on special populations <65 years who are eligible for the program. The ICES Physician Database provides information on physician specialty. Emigration from the province was the only reason for loss to follow-up (0.5 % per year) [15].

Primary cohort

Kidney transplant recipients

We included all adults (age ≥ 18 years) with a first kidney transplant from July 1, 1994 to December 31, 2009. We defined the date of the kidney transplant as the date of cohort entry (also referred to as the index date).

Reference cohorts

To put the frequency of BMD testing into context, we matched recipients on age (±1 year), sex, and index date (±1 year) to two non-transplant reference cohorts; one group was considered to be at a low fracture risk where we would not expect frequent testing and one group was at an increased fracture risk where we would expect more frequent testing. Specifically, we matched recipients to the general population with no previous non-vertebral fracture (low fracture risk) (defined as proximal humerus, forearm, hip) and the general population with a previous non-vertebral fracture (increased fracture risk). When permitted by the available sample, we matched one recipient to four persons from the non-transplant reference cohort. Further detail on the cohort creation for these reference groups has been described elsewhere [4]. In Ontario, the 3-year incidence of fracture is higher in individuals with a previous non-vertebral fracture than in kidney transplant recipients (of which 1.6 % have a non-vertebral fracture [proximal humerus, forearm, hip] post-transplant) [4].

Outcomes

We used physician fee-for-service billings to identify BMD by dual energy X-ray absorptiometry and, prior to April 1998, dual-photon absorptiometry tests (Additional file 1) [16]. In Ontario, these data are largely complete with approximately 94 % of physicians submitting such billing [17]. These BMD billing codes have been successfully used in several prior studies [18, 19]. We tabulated the number of BMD tests in the 3 years following kidney transplantation; multiple billings for a BMD test for a given person on the same day were counted as one test. We selected a 3-year follow-up to allow enough time for recipients to undergo multiple BMD tests; Osteoporosis Canada guidelines recommend a repeat BMD test in the 1–3 years after the initial test [9]. To calculate the total cost of the BMD tests, we included all associated billings (technical component of the test and professional component [e.g. physician interpreting the BMD test]) and accounted for inflation; additional information on billings can be found in Additional file 2.

Statistical analysis

We used medians (interquartile range [IQR]) or means (standard deviation) to summarize baseline characteristics for continuous data and proportions to summarize categorical data. To compare baseline characteristics between recipients with at least one BMD test to those without a BMD test, we used the chi-square, Mann-Whitney U test, or Student's t test as appropriate. We stratified the frequency of BMD testing by sex (men versus women) and age at the time of transplantation (<50 versus ≥50 years). We selected this age dichotomization for several reasons: kidney transplant recipients aged >50 years are at an increased fracture risk compared to younger recipients [4, 20]; favourable statistical properties (median age of our cohort was 50 years); and Osteoporosis Canada guidelines recommend BMD testing in individuals aged 50–64 years who have clinical risk factors for fracture (e.g. prolonged high-dose glucocorticoid use) [9]. We used logistic regression to determine if there was a statistically significant difference across transplant centres in the decision to perform at least one BMD test after transplantation. We adjusted for covariates that may influence a physician's decision to order a BMD test (age, sex, previous non-vertebral fracture, and comorbidities [as measured by the Charlson comorbidity index [21]]). To determine if there were changes over time in the number of BMD tests performed, we used the Cochran-Armitage test for trend. To compare the number of recipients who had at least one BMD test to the matched non-transplant reference groups, we used McNemar's test. We considered a two-sided p value <0.05 as statistically significant. We performed all analyses using the Statistical Analysis Software (SAS version 9.3).

Results

Baseline characteristics

We included 4821 kidney transplant recipients with a total observational time of 13,943 person-years; 304 (6.3 %) recipients died within 3 years. Comparing recipients who had at least one BMD (n = 2786) to recipients who did not (n = 2035), recipients with at least one BMD were significantly more likely to be women (42.4 versus 29.4 %; P < 0.001) and to have received a transplant in the later years of cohort entry (39.3 versus 25.5 %; P < 0.001); there was no significant difference in history of a previous non-vertebral fracture prior to transplant (2.4 versus 2.0 %) (Table 1). Matching characteristics were similar between recipients and the non-transplant reference groups (Additional file 3).

Table 1

Baseline characteristics of kidney transplant recipients classified by presence of at least one bone mineral density test in the 3 years after transplantation^a

	Bone mineral density test

Characteristic	Yes	No	P value
	(n = 2786)	(n = 2035)
Age, years	50 (39–59)	49 (38–59)	0.04
Women	1182 (42.4 %)	599 (29.4 %)	<0.001
Transplant era			<0.001
1994–1997	290(104%)	624 (30.7 %)
1998–2001	631 (22.6 %)	480 (23.6 %)
2002–2005	769 (27.6 %)	413 (20.3 %)
2006–2009	1096 (39.3 %)	518 (25.5 %)
Diabetes	690 (24.8 %)	565 (27.8 %)	0.02
Previous non-vertebral fracture	68 (2.4 %)	41 (2.0 %)	0.33
Charlson comorbidity index^b	2.6 ± 1.0	2.7 ± 1.2	0.002

Data are median (interquartile range), mean (± SD) or numbers (percent)

Abbreviation: SD standard deviation

Age and transplant era were assessed at the time of transplant (index date).

Diabetes and Charlson comorbidity index were assessed in the 3 years prior to the transplant date. Prior non-vertebral fracture was defined as a composite of proximal humerus, forearm, hip fractures from 1991 to transplant date (index date)

All recipients with a Charlson comorbidity index (CCI) of 0 were given a score of 2 and those with a score of 1 were given a score of 3; one of the variables in the CCI is presence of end-stage renal disease which automatically results in recipients receiving a score of 2

Bone mineral density

Approximately 58 % (n = 2786) of kidney transplant recipients underwent at least one BMD test within 3 years of receiving their transplant and 22 % (n = 1047) of recipients underwent a BMD test in the 3 months following transplant. Among those with at least one BMD test, the median time after transplant to first BMD was 133 days (IQR 62–372 days). A total of 68.1 % of female recipients aged >50 years underwent a BMD test, a higher proportion than the other three age and sex strata (P < 0.005) (Table 2). There were a total of 4802 BMD tests (median 1, range 0–6 tests per recipient) and almost one third (31.7 %) of recipients underwent more than one BMD test in the 3 years after transplant (Additional file 4). The total cost of these tests was $614,997 (CAD 2014 equivalent dollars) (approximately $128 per recipient) across the 18-year study period. The proportion of recipients who underwent at least one BMD test in follow-up varied from 15.6 to 92.1 % (P < 0.001) across the six Ontario transplant centres. The variation across transplant centres persisted after adjustment for recipient age, sex, history of previous non-vertebral fracture, and comorbidities (logistic regression model, P < 0.001). When information on the ordering physician was available (96 % of tests), BMD tests were most commonly ordered by nephrologists (67.8 %) and family physicians (16.5 %), followed by general internists (5.0 %), rheumatologists (3.4 %), and endocrinologists (2.4 %).

Table 2

Number (proportion) of kidney transplant recipients with at least one bone mineral density test in the 3 years after transplantation by age and sex

	Kidney transplant recipients
	(n = 4821)
Overall	2786 (57.8 %)
Women <50 years	612 (64.8 %)
Women ≥50 years	570 (68.1 %)
Men <50 years	741 (50.7 %)
Men ≥50 years	863 (54.7 %)

Non-transplant reference groups

In the general population with a previous non-vertebral fracture (n = 4821), there were 863 BMD tests (range 0–4) in the 3 years after the index date compared to 4802 BMD tests in the recipient population. In the general population with no previous non-vertebral fracture (n = 19,284), there were 1936 BMD tests (range 0–4). There were a significantly higher number of kidney transplant recipients with at least one BMD (58 %) in the 3-year follow-up versus both matched reference groups (13.8 % general population with a previous non-vertebral fracture and 8.5 % general population with no previous non-vertebral fracture, respectively, P < 0.001 for each paired comparison) (Table 3). Individuals who had an index date (cohort entry date) in more recent years were more likely to have underwent at least one BMD test in follow-up (recipients who transplanted in 1994, 20.9 and 66.4 % in 2009; general population with a previous non-vertebral fracture, 3.5 % in 1994 and 15.6 % in 2009; general population with no previous non-vertebral fracture, 2.6 % in 1994 and 8.5 % in 2009; P for trend <0.001) (Fig. 1).

Fig. 1

Kidney transplant recipients, individuals from the general population with a previous non-vertebral fracture and individuals from the general population with no previous non-vertebral fracture with at least one bone mineral density test in the 3 years after cohort entry, presented by year of cohort entry (P for trend <0.001 for all three cohorts)

Table 3

Number (proportion) of kidney transplant recipients with at least one bone mineral density test in the 3 years of follow-up compared to several reference groups matched on age, sex, and index date

Population	N (%)	P value^*
Kidney transplant recipients (n = 4821)	2786 (57.8 %)	Reference
General population with no previous non-vertebral fracture (n = 19,284)	1645 (8.5 %)	<0.001
General population with a previous non-vertebral fracture (n = 4821)	665 (13.8 %)	<0.001

Matched on age (±1 year), sex, and index date (±1 year)

Paired P value

Bisphosphonates

Of the 3540 recipients who had prescription drug coverage through universal healthcare benefits, 646 (18.2 %) were prescribed bisphosphonates. Of recipients prescribed bisphosphonates, 548 (84.8 %) of these prescriptions were filled at a median of 57 days (IQR 21 to 175 days) after the BMD test, with 417 receiving a bisphosphonate prescription in the first 6 months after a BMD test.

Discussion

In Ontario, Canada, we found that over half of the kidney transplant recipients underwent at least one BMD test in the subsequent 3 years after transplant, and many recipients underwent multiple tests. The frequency of BMD testing varied widely by centre—from as few as 15 % of recipients undergoing a BMD test to as many as 92 %, and this variability was not explained by recipient characteristics. Kidney transplant recipients were significantly more likely to undergo a BMD compared to two matched non-transplant reference groups. Our results suggest that BMD testing is commonly performed in kidney transplant recipients despite weak evidence in the literature supporting its widespread use.

The results of our population-based multicentre study extend the findings of two prior single centre reports with smaller sample sizes. In the first study of kidney transplant recipients (n = 326) from Manitoba, Canada, almost 60 % of recipients were found to have had at least two BMD tests within approximately 8 years of their transplant [22]. The second study from Akaberi et al. found that 670 BMD tests were performed in 238 kidney transplant recipients (75 % had at least two BMD tests) from Sweden over 12 years [12]. The centres in these two prior studies had protocols in place for routine BMD testing, and so the frequency of BMD testing would be expected to be high. In contrast, in our study, only a few of the transplant programs had a protocol for BMD testing (information provided by the six Ontario transplant centres, personal communication).

Particularly striking is the high number of kidney transplant recipients who underwent multiple BMD tests in the 3 years after transplantation, at a high cost to the healthcare system. For example, almost one third of kidney transplant recipients underwent two or more BMD tests within 3 years of their transplant; in the non-transplant population, the benefits of performing multiple BMD tests over several years have been questioned [23, 24], especially given the increasing knowledge of unwarranted screening harms [25, 26].

The benefit of BMD tests in kidney transplant recipients remains uncertain. First, the utility of BMD in predicting fracture in kidney transplant recipients is unclear [12 –14]. For example, the Kidney Disease Improving Global Outcomes (KDIGO) guidelines for CKD-MBD suggest that patients with an estimated glomerular filtration rate >30 mL/min/1.73 m² have their BMD assessed in the first 3 months after kidney transplant if they received glucocorticoids or have other risk factors for osteoporosis [8]. However, given the limited evidence, this suggestion was given the weakest grade of evidence [8]. It is important to note that this recommendation is currently being reassessed in the revised version of the guidelines [27] in light of recent evidence finding that BMD may be predictive of fracture in individuals with CKD, including dialysis [28, 29]; however, there is still conflicting evidence in kidney transplant recipients [12 –14]. Second, given the high incidence of adynamic bone disease (i.e. low turnover) in kidney transplant recipients, the KDIGO guidelines suggest that a bone biopsy may be needed to guide treatment decisions; this limits the clinical usefulness of BMD testing post-transplant [8]. Third, and perhaps most relevant, recent research suggests in contrast to what has been previously reported, most kidney transplant recipients will not fracture and have an average mean BMD for age and sex [4, 5, 12, 22, 30]. Note, however, that the lower than expected fracture incidence and normal BMD may be the result of increased monitoring of bone health after transplant. Taken together, this suggests there may be little need to perform BMD tests routinely.

It is important to note that BMD testing may alter clinical practice. Many transplant recipients were prescribed a bisphosphonate in the first 6 months after receiving a BMD test. However, the efficacy of this and other fracture prevention strategies in kidney transplant recipients remains uncertain [31].

We make several recommendations based on the findings in this study. First, given the uncertainty that exists in the ability of BMD to predict fracture in kidney transplant recipients, new measures that have been found to predict fracture independent of BMD should be examined. For example, the trabecular bone score assesses bone quality (microarchitecture) and has been found to predict fracture in the general population [32 –34]. This measure could be useful at predicting fracture in kidney transplant recipients given bone quality is particularly affected in recipients with CKD-MBD [8]. Second, new high-quality information from prospective observational studies and clinical trials is needed to guide the optimal recommended timing and frequency of BMD testing. Such studies should also assess the ability of BMD to predict fracture and its cost-effectiveness.

Our study has some limitations. First, we did not have drug dispensing information for the entire transplant cohort (only those who were covered by provincial drug benefits). While we were unable to characterize immunosuppression use at the patient level, during the time frame of this study, steroids were nearly universally prescribed at the Ontario transplant centres. Second, we only knew if a BMD was done, without information on the BMD value. However, the former supported the primary objective of this study—to determine the frequency of BMD testing in the first 3 years after transplant across several kidney transplant centres. Third, due to the low number of fracture events, we were not able to determine if transplant centres with more BMD tests had fewer fracture events. Moreover, the small number of recipients with a previous non-vertebral fracture may have limited our statistical power to determine whether recipients with a previous fracture were more likely to undergo a BMD test. Fourth, the variability in BMD testing we observed across transplant centres was in the setting of universal healthcare benefits. It is possible that these results may not generalize to other types of healthcare systems; variability across transplant centres might be even greater in jurisdictions without such healthcare benefits, as economic factors may also influence testing. Finally, we did not assess the impact of the KDIGO CKD-MBD guidelines on BMD testing. However, this guideline received the weakest grade of evidence; therefore, its uptake would likely be variable across transplant centres as demonstrated in this study.

Conclusions

Many kidney transplant recipients underwent a BMD test in the 3 years after transplantation despite the lack of evidence to suggest BMD can accurately predict fracture. These results highlight the need for further studies to understand the utility, frequency, timing, and cost-effectiveness of BMD testing in kidney transplant recipients.

Additional files

Additional file 1: Database codes for bone mineral density tests. (PDF 83 kb)

Additional file 2: Supporting methods. (PDF 143 kb)

Additional file 3: Baseline characteristics of reference groups. (PDF 202 kb)

Additional file 4: Frequency of bone mineral density tests performed in kidney transplant recipients. (PDF 140 kb)

Footnotes

Abbreviations:

William Leslie: Speaker bureau: Amgen, Eli Lilly, Novartis. Research grants: Amgen, Genzyme. Jonathan Adachi: Speaker/Consultant: Amgen, Eli Lilly, Merck, Novartis, Warner Chilcott. Clinical Trials: Amgen, Eli Lilly, Merck, Novartis. Greg Knoll has received investigator-initiated research grants from Astellas, Pfizer, Roche and Novartis. Amit Garg received an investigator-initiated grant from Astellas and Roche for a Canadian Institutes of Health Research study in living kidney donors. The other authors declare that they have no competing interests.

KLN and AXG conceived the study and participated in its design and coordination. KLN performed the statistical analysis and drafted the manuscript. All authors read and approved the final manuscript.

Acknowledgements

Dr. Naylor is supported by the Canadian Institutes of Health Research Fellowship and the Canadian National Transplant Research Program Astellas Training Award. Dr. Lam is supported by a KRESCENT new investigator award. Dr. Garg was supported by the Dr. Adam Linton Chair in Kidney Health Analytics. This study was supported by the Institute for Clinical Evaluative Sciences (ICES), which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). The opinions, results, and conclusions reported in this paper are those of the authors and are independent from the funding sources. No endorsement by ICES or the Ontario MOHLTC is intended or should be inferred. Parts of this material are based on data and information compiled and provided by CIHI. However, the analyses, conclusions, opinions, and statements expressed herein are those of the author, and not necessarily those of CIHI.

References

Ramsey-Goldman

Dunn

Dunlop

Stuart

Abecassis

Kaufman

Increased risk of fracture in patients receiving solid organ transplants. Journal of Bone & Mineral Research. 1999;14:456–63.

Abbott

Oglesby

Hypolite

Kirk

Welch

Hospitalizations for fractures after renal transplantation in the United States. Ann Epidemiol. 2001;11:450–7.

Vautour

Melton

ILJ

Clarke

Achenbach

Oberg

McCarthy

JT.

Long-term fracture risk following renal transplantation: a population-based study. Osteoporos Int. 2004;15:160–7.

Naylor

Jamal

Zou

McArthur

Lam

Leslie

Fracture incidence in adult kidney transplant recipients. Transplantation. 2015;100 (1):167–75.

Naylor

Leslie

Hodsman

Rush

Garg

AX.

FRAX predicts fracture risk in kidney transplant recipients. Transplantation. 2014;97:940–5.

Grossman

Gordon

Ranganath

Deal

Caplan

Chen

American College of Rheumatology 2010 recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care Res (Hoboken). 2010;62:1515–26.

National Osteoporosis Foundation. Clinicians guide to prevention and treatment of osteoporosis. Washington, DC: National Osteoporosis Foundation; 2010.

KDIGO Work Group. KDIGO clinical practice guidelines for the prevention, diagnosis, evaluation, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int. 2009;S113:S1–S130.

Papaioannou

Morin

Cheung

Atkinson

Brown

Feldman

2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary. CMAJ. 2010;182:1864–73.

10.

Johnell

Kanis

Oden

Johansson

De Laet

Delmas

Predictive value of BMD for hip and other fractures. J Bone Miner Res. 2005;20:1185–94.

11.

Marshall

Johnell

Wedel

Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ. 1996;312:1254–9.

12.

Akaberi

Simonsen

Lindergard

Nyberg

Can DXA predict fractures in renal transplant patients? Am J Transplant. 2008;8:2647–51.

13.

Grotz

Mundinger

Gugel

Exner

Kirste

Schollmeyer

PJ.

Bone fracture and osteodensitometry with dual energy X-ray absorptiometry in kidney transplant recipients. Transplantation. 1994;58:912–5.

14.

Durieux

Mercadal

Orcel

Dao

Rioux

Bernard

Bone mineral density and fracture prevalence in long-term kidney graft recipients. Transplantation. 2002;74:496–500.

15.

Ontario Ministry of Finance. Ontario population projections update 2012–2036. Toronto: Government of Ontario; 2013.

16.

Ontario Ministry of Health and Long term Care. Schedule of benefits. Ontario: Queen's Printer; 2014.

17.

Institute for Clinical Evaluative Sciences. Improving health care data in Ontario. Toronto: ICES; 2005.

18.

Jaglal

McIsaac

Hawker

Jaakkimainen

Cadarette

Chan

BT.

Patterns of use of the bone mineral density test in Ontario, 1992–1998. CMAJ. 2000;163:1139–43.

19.

Cadarette

Jaglal

Raman-Wilms

Beaton

Paterson

JM.

Osteoporosis quality indicators using healthcare utilization data. Osteoporos Int. 2011;22:1335–42.

20.

Nikkel

Mohan

Zhang

McMahon

Boutroy

Dube

Reduced fracture risk with early corticosteroid withdrawal after kidney transplant. Am J Transplant. 2012;12:649–59.

21.

Charlson

Pompei

Ales

MacKenzie

CR.

A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40:373–83.

22.

Naylor

Garg

Hodsman

Rush

Leslie

WD.

Long-term changes in bone mineral density in kidney transplant recipients. Transplantation. 2014;98:1279–85.

23.

Hillier

Stone

Bauer

Rizzo

Pedula

Cauley

Evaluating the value of repeat bone mineral density measurement and prediction of fractures in older women: the study of osteoporotic fractures. Arch Intern Med. 2007;167:155–60.

24.

Gourlay

Fine

Preisser

May

Lui

Bone-density testing interval and transition to osteoporosis in older women. N Engl J Med. 2012;366:225–33.

25.

Moyer

VA.

Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2012;157:120–34.

26.

Sasieni

Castanon

Cuzick

Effectiveness of cervical screening with age: population based case-control study of prospectively recorded data. BMJ. 2009;339:b2968.

27.

Ketteler

Elder

Evenepoel

Jamal

Lafage-Proust

Revisiting KDIGO clinical practice guideline on chronic kidney disease-mineral and bone disorder: a commentary from a Kidney Disease: Improving Global Outcomes controversies conference. Kidney Int. 2015;87:502–28.

28.

Iimori

Mori

Akita

Kuyama

Takada

Asai

Diagnostic usefulness of bone mineral density and biochemical markers of bone turnover in predicting fracture in CKD stage 5D patients—a single-centre cohort study. Nephrol Dial Transplant. 2012;27:345–51.

29.

Yenchek

Shlipak

Bauer

Rianon

Kritchevsky

Bone mineral density and fracture risk in older individuals with CKD. Clin J Am Soc Nephrol. 2012;7:1130–6.

30.

Carlini

Rojas

Weisinger

Lopez

Martinis

Arminio

Bone disease in patients with long-term renal transplantation and normal renal function. Am J Kidney Dis. 2000;36:160–6.

31.

Palmer

McGregor

Strippoli

GFM.

Interventions for preventing bone disease in kidney transplant recipients. Cochrane Database Syst Rev. 2009;4:1.

32.

Boutroy

Hans

Sornay-Rendu

Vilayphiou

Winzenrieth

Chapurlat

Trabecular bone score improves fracture risk prediction in non-osteoporotic women: the OFELY study. Osteoporos Int. 2013;24:77–85.

33.

Rabier

Heraud

Grand-Lenoir

Winzenrieth

Hans

A multicentre, retrospective case-control study assessing the role of trabecular bone score (TBS) in menopausal Caucasian women with low areal bone mineral density (BMDa): analysing the odds of vertebral fracture. BOne. 2010;46:176–81.

34.

Hans

Goertzen

Krieg

Leslie

WD.

Bone microarchitecture assessed by TBS predicts osteoporotic fractures independent of bone density: the Manitoba study. J Bone Miner Res. 2011;26:2762–9.