bs_bs_banner
doi:10.1111/jpc.12789
ORIGINAL ARTICLE
Bone density assessment in a tertiary paediatric centre over 13 years: Referral patterns and limitations Alicia R Jones,1,2 Margaret R Zacharin,2,3 Fergus J Cameron2,3 and Peter J Simm2,3 1
The Alfred Hospital, 2Department of Endocrinology and Diabetes, Royal Children’s Hospital, and 3Centre for Hormone Research, Murdoch Children’s Research Institute, Melbourne, Victoria, Australia
Aim: This study aims to examine the referral practices for the Royal Children’s Hospital (RCH) bone density service over the past 13 years and to demonstrate referral patterns and possible limitations to accessing paediatric bone densitometry. Methods: All patients attending the RCH Healthy Bones Unit for bone densitometry from 1 July 1999 to 30 June 2012, aged under 18 years of age, were included. Densitometry results were downloaded directly from the Hologic scanner into an Excel document. However, the referring unit and indication for referral were collected manually from either the referral card or the hospital’s scanned medical records system. Results: A total of 5767 bone densitometry scans were performed over the study period on 3004 patients. The majority of referrals were made by the Endocrinology department, followed by Adolescent Medicine, Gastroenterology and Neurology. Relatively few referrals were made by general paediatrics. The most common indication for bone density test overall was eating disorders, followed by steroid use, osteogenesis imperfecta and other collagen disorders and inflammatory bowel disease. The lowest lumbar spine z-scores by indication were for cerebral palsy and other causes of immobility. Conclusions: Multiple childhood diseases predispose to low bone density; however, paediatric bone densitometry is still underutilised and not appropriately supported by subsidies. Key words:
DXA; paediatrics bone density; skeletal fragility.
What is already known about this topic
What this paper adds
1 Osteoporosis is a leading cause of morbidity within Australia. 2 Failure to achieve peak bone mass in childhood predisposes to later osteoporosis. 3 Disorders of childhood such as cerebral palsy, chronic immobility, eating disorders, osteogenesis imperfecta and steroid use can cause low bone density and fragility fractures with high concurrent morbidity.
1 Many paediatric indications for bone densitometry are not covered by current Medicare subsidies. 2 Awareness of bone health issues is still variable even in a tertiary setting. 3 Patients with immobility have the lowest bone densities across all indications for scanning but are not recognised by the Medicare system as an indication for scanning.
Osteoporosis is a leading cause of morbidity within Australia, affecting an estimated 3% of the overall population.1 Osteoporosis in adulthood predisposes to fracture, increased disability and reduced quality of life.2–4 Rates of osteoporosis increase with age; however, it has been described as a ‘Paediatric disease with geriatric consequences’.5 This is because over 90% of peak bone mass is accrued by the age of 18,6 and failure to achieve an adequate peak bone mass during adolescence has been linked with later development of Correspondence: Dr Alicia Jones, Department of Endocrinology and Diabetes, Royal Children’s Hospital, 50 Flemington Road, Parkville VIC 3052 Australia. Fax: (03) 9345 6240; email: [email protected] Conflict of interest: The authors declare they have no conflicts of interest in relation to this manuscript Research carried out at The Royal Children’s Hospital, 50 Flemington Road, Parkville, 3052 Accepted for publication 21 October 2014.
608
osteoporosis.7 Unfortunately, the prevalence of impaired bone mass accrual in children is poorly understood. Osteoporosis in childhood is classified as primary or secondary (see Table 1).9 The International Society for Clinical Densitometry (ISCD) states that osteoporosis should not be diagnosed in children on the basis of low bone densitometry alone. Rather, the combination of low bone mineral density (BMD; z-score ≤ −2.0) and a clinically significant fracture allows this diagnosis to be reached.8 Furthermore, interpretation of densitometric data in paediatrics is difficult as the ‘normal’ BMD value changes with age, pubertal status and body size. However, dual-energy X-ray absorptiometry (DXA) remains the gold standard for assessing bone density in childhood, with a welldescribed correlation between DXA findings and fracture risk.9 The Royal Children’s Hospital (RCH) Healthy Bones Unit has been performing DXA scans since 1999 and is the main paediatric bone density service in Victoria. The ISCD has published guidelines on the indications and frequency of densitometry
Journal of Paediatrics and Child Health 51 (2015) 608–613 © 2015 The Authors Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians)
AR Jones et al.
Referral patterns for paediatric bone density
Table 1 Causes of osteoporosis in children and adolescents (adapted from ISCD guidelines8) Primary causes
Secondary causes
Osteogenesis imperfecta Idiopathic juvenile osteoporosis Ehler–Danlos syndrome Marfan syndrome
Immobility Cerebral palsy Duchenne muscular dystrophy Paraplegia Chronic inflammatory diseases Inflammatory bowel disease Cystic fibrosis Nutritional Vitamin D deficiency/rickets Malabsorption Coeliac disease Hypogonadism Eating disorders Endocrine disturbances Chronic liver disease Chronic renal disease Drug-related: glucocorticoids, warfarin, anticonvulsant medications, chemotherapy
testing8; however, the level of evidence for these recommendations varies, and as many indications are not supported by Medicare subsidies, it is likely that the service is underutilised. The aim of this study was to examine the referral practices for the RCH bone density service over the past 13 years, in order to define which departments refer, for which indications, and trends over time. It is hoped this will help to identify boundaries to optimal utilisation of DXA in paediatric medicine.
Fig. 1 Number of DXA scans by year. , total densitometry scans performed, number per year; , new referrals, number per year.
of birth, gender, scan date and age/weight/height at time of scan, and DXA results. Adjusting for height is performed after Ward et al. if in the appropriate age and height range for these reference data, whereas bone age adjustment is also undertaken if feasible.10 The referrer and indication for referral were extracted manually directly from each referral card, or where information on the referral was missing from the hospital’s scanned medical records system.
Statistical analysis Data were processed using Microsoft Excel for Mac 2008, version 12.3.6. Data were described as mean and range for both raw data and percentages, grouped initially by year then as a total of the entire study period.
Results Methods Setting The study was carried out at The RCH in Melbourne, a tertiary paediatric hospital that is the main centre for paediatric bone density testing in the state of Victoria. The RCH Healthy Bones Unit has been performing DXA scans since July 1999, using an Hologic QDR 4500 scanner (Hologic Inc., Bedford, MA, USA).
Participants All patients attending the RCH Healthy Bones Unit for DXA scans from July 1, 1999 to June 30, 2012 were included. Patients who were aged >18 years at time of scan were excluded, as were all those referred for DXA purely for research purposes (Hologic Inc., Bedford, MA, USA).
Data collection All DXA tests performed between the dates above were downloaded from the Hologic scanner and converted directly into an Excel document. Data included were the patient ID, name, date
A total of 5767 bone densitometry scans were performed over the study period on 3004 patients. The total number of referrals and new referrals by year were depicted in Figure 1. Although the total number of referrals increased over the study period, the number of new referrals remained relatively stable from 2000 to 2012. The endocrinology unit made the majority of referrals (2545, 44.1% of all referrals) over the entire study period and each year (see Fig. 2). However, the percentage of referrals each year made by endocrinology declined. There was an increase in the percentage of referrals from adolescent medicine (2.8% in 1999–2000, 15.2% in 2011–2012), haematology (0.5% in 1999–2000, 11.3% in 2011–2012) and neurology (0.9% in 1999–2000, 8.3% in 2011–2012) as a total of all referrals over the study period; however, referrals from the general paediatrics and other departments remained relatively stable over time. The most common indication for bone density test overall was eating disorders (743 referrals), followed by steroid use (670 referrals), osteogenesis imperfecta and other collagen disorders (614 referrals), and inflammatory bowel disease (531 referrals) (see Fig. 3). Over time, there was an increase in the percentage of referrals made for eating disorders, immobility (other) and
Journal of Paediatrics and Child Health 51 (2015) 608–613 © 2015 The Authors Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians)
609
Referral patterns for paediatric bone density
Fig. 2
AR Jones et al.
Referrals by unit. No legend; raw numbers of referrals per year by unit.
warfarin. There was a decrease in referrals for steroid use, hypogonadism and cystic fibrosis. Data were unable to be obtained for 15 referring units and 69 indications. The average lumbar spine z-score for the primary indications is depicted in Table 2. The lowest average z-score was for cerebral palsy (z –2.4), followed by immobility due to paraplegia and immobility due to other causes. The number of patients receiving a repeat DXA scan, interval between scans and number of scans per patient for the main indications is listed in Table 3.
Discussion To our knowledge, this is the largest audit of paediatric bone density testing. It highlights a number of complex issues in paediatric bone mass assessment. Although other options for assessing bone mass and strength exist such as peripheral quantitative computerised tomography, DXA scanning is still the most widely available modality with the best paediatric reference data and correlations with fracture risk.8,9 This modality has been used at The RCH since 1999. Over 90% of peak bone mass is achieved during childhood and adolescence. Appendicular longitudinal bone growth is rapid after birth and accelerates until puberty when appendicular bone growth slows and axial growth accelerates. Exposure to risk factors before and during puberty negatively affects this growth, resulting in a lower peak cortical thickness. This predisposes to lower adult BMD.11 Indeed, several studies have linked childhood disease with lower bone density in adulthood. French et al. studied 32 adult patients with a history of juvenile chronic arthritis before the age of 16 years and found 610
that a substantial proportion were osteopenic.12 Similarly, Finkelstein et al. studied 23 adult men with a history of delayed puberty and found that compared with controls they had significantly reduced bone density.13 Longitudinal studies of patients with eating disorders demonstrate long-term reductions in bone density 10–20 years following recovery.14,15 Osteoporosis was estimated to cost the Australian healthcare system $1.9 billion per year in direct costs and an additional $5.6 billion in indirect costs in the year 2000–2001.16 Prevention of osteoporosis, starting in childhood and focusing on optimising bone accrual rather than just reacting to losses later in life should thus be a high public health priority. Unfortunately, there are multiple barriers to diagnosing low bone density in paediatrics, and the service is relatively underutilised and children remain undiagnosed and untreated. These barriers include low referral rates, poor knowledge among medical professionals of interpretation of data, optimal timing of follow-up scans and the cost of bone densitometry, which in Australia is only subsidised if the indication meets one of five criteria specific by Medicare (see Table 4). Another difficulty in managing paediatric low bone density is how a clinician should respond to a low DXA result. Although there is good evidence for use of bisphosphonate therapy in adults, there is a lack of long-term data on the efficacy and safety of bisphosphonates in children and adolescents.17 As such if a BMD is found to be low/falling, a clinician needs to explore issues such as fracture history, immobility, diet and other preventative strategies, before considering bisphosphonate therapy. This study did not examine bisphosphonate use or the relation of this to BMD results. Cerebral palsy and chronic immobility are well-established causes of low BMD, with greater levels of immobility associated
Journal of Paediatrics and Child Health 51 (2015) 608–613 © 2015 The Authors Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians)
AR Jones et al.
Fig. 3
Referral patterns for paediatric bone density
Referrals by indication. No legend; raw numbers of referrals per year by indication.
with higher risk of low bone density.18–20 Our study supports previous reports, with the lowest average z-scores for the indications of cerebral palsy, paraplegia and other causes of immobility. Despite this well-known link between immobility and low bone density, there is still no Medicare code of funding for bone density testing in cases of immobilisation. The closest indication funded by Medicare is for a fragility fracture. It would clearly be preferable to diagnose low bone density before a fracture has occurred, thus permitting appropriate management strategies to be introduced to improve BMD and reduce fracture risk where possible. Furthermore, decisions as to the type, timing and duration of interventions for low impact fractures in these patients are also determined by changes in BMD. Thus, sequential testing is often beneficial and relies on a baseline measure with which to compare. Eating disorders are also a well-established cause of low bone density. It is recommended that patients with an eating disorder
Table 2
Average lumbar spine z-score by indication
Indication
Average z-score (range)
Cerebral palsy Immobility – paraplegia Immobility – other Hypogonadism Eating disorder Osteogenesis imperfecta Medication – steroid Medication – warfarin Fracture Inflammatory bowel disease Cystic fibrosis
−2.4 (−6.0, 3.6) −1.90 (−6.8, 0.1) −1.8 (−5.8, 2.4) −1.0 (−7.0, 2.6) −0.8 (−4.9, 2.6) −0.9 (−6.2, 2.5) −1.1 (−4.7, 2.5) −1.2 (−3.5, 2.7) −1.2 (−5.6, 2.3) −1.2 (−4.4, 2.7) −1.2 (−4.4, 2.0)
Journal of Paediatrics and Child Health 51 (2015) 608–613 © 2015 The Authors Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians)
611
Referral patterns for paediatric bone density
AR Jones et al.
Table 3 Interval for repeat DXA scan by indication Indication
Patients with repeat scan, n (%)
Average interval for repeat scan, months
Number of scans per individual, median (range)
Cerebral palsy Hypogonadism Eating disorder Osteogenesis imperfecta Medication – glucocorticoids Medication – warfarin Inflammatory bowel disease Cystic fibrosis
58 (22.83) 64 (20.71) 63 (8.48) 89 (14.50) 149 (22.24) 92 (25.27) 119 (22.41) 95 (23.40)
17.29 21.09 15.40 13.30 19.69 21.30 16.45 22.77
2 (1–10) 1 (1–6) 1 (1–6) 4 (1–14) 1 (1–9) 2 (1–8) 1 (1–9) 2 (1–10)
Table 4 Medicare subsidised indications for bone densitometry Medicare code
Indication
12306
Confirmation or presumptive diagnosis of low bone mineral density made on the basis of one or more fractures occurring after minimal trauma, or monitoring of low bone density proven by densitometry at least 12 months prior Diagnosis and monitoring of bone loss associated with prolonged glucocorticoid therapy, excess glucocorticoid secretion, male hypogonadism, female hypogonadism lasting more than 6 months before age 45 Diagnosis and monitoring of bone loss associated with primary hyperparathyroidism, chronic liver disease, chronic renal disease, proven malabsorptive disorders, rheumatoid arthritis, thyroxine excess. Measurement 12 months following a significant change in therapy for established low bone mineral density or presumptive lone bone mineral density following a minimal trauma fracture Screening patients over 70 years of age
12312
12315
12321
12323
and associated amenorrhoea of 6–12 months duration have a bone densitometry,21 as hypogonadism and other factors negatively impact bone mass. In our study, it was reassuring to see that the number of referrals for eating disorder increased with time, as has the prevalence and awareness of eating disorders. Performing BMD testing in these patients while young enables introduction of interventions to increase bone mass, which may assist in attaining a normal peak bone mass, thus reducing the risk of later osteoporosis. Another significant risk factor for low bone density in children is medication use. Exogenous glucocorticoids are a known cause of osteoporosis; however, other medications such as warfarin,22 depo provera23 and anticonvulsants24 have also 612
been linked with low bone density. Although official guidelines are lacking, National and international groups such as Osteoporosis Australia and the National Osteoporosis Foundation recognise these medications as risk factors for osteoporosis, and it is recommended that children on these medications long-term have bone densitometry to detect, monitor and potentially treat low bone density. It is fitting then that in our study, the number of referrals for warfarin increased over the time period. However, the number of referrals for other medications remained very low, with a total of only 46 referrals over the entire study. Possible causes of this may be a lack of awareness of the adverse effects of these medications among health professionals and the lack of funding to subsidise scans for this indication. The ISCD states that the minimum interval for repeating a bone measurement to monitor treatment with a bone-active agent or disease process is 6 months.8 In our study, the average interval for a repeat scan was greater than this, with the shortest average interval of 13 months for osteogenesis imperfecta. Although many patients will not need a repeat scan in a shorter time frame, some children with actively growing bones, more rapidly developing disease and use of medications that alter bone mass may benefit from more regular densitometry. Again, funding issues limit the number of scans undertaken, as currently only one scan every 12 or 24 months is funded depending on the indication. Although this may be appropriate for adults with slowly progressing disease, it is less appropriate for children and not in line with international standards. There are several limitations to our study. Departmental referral numbers will skew data related to referring units. Furthermore, many complex patients may be seen in more than one department and may have more than one indication for bone densitometry. For example, many patients with inflammatory bowel disease are also on steroids. Thus, the unit and indication listed on the card may not encompass the whole picture of the patient. A further limitation is that we did not analyse femoral BMD. As per the ISCD 2013 official position statement, the hip is not a preferred measurement site in growing children due to variability in skeletal development.8 However, some studies have demonstrated that there is significant deviation between proximal femur and lumbar spine BMD measurements in paediatric patients.25,26 This could confer an increased lower limb fracture risk, which would not be identified without the use of femoral z-scores. In children with conditions such as cerebral palsy and muscular dystrophy, contractures and deformities make positioning for proximal hip DXA difficult, as such the femoral neck, total hip and other measures of proximal femur are less reliable.25 To overcome these difficulties, some authors have suggested using distal femur BMD measurements, which appear to have more accuracy than proximal femur, as a marker of increased fracture risk.26,27 Unfortunately, our institution does not measure distal femur BMD. Finally, the data for the indication for referral were missing for 69 patient events. Patient information is essential to the accurate interpretation of BMD testing. This demonstrates an important gap in referrer education and necessarily limits reporting and data interpretation, thus reducing information for the referring physician.
Journal of Paediatrics and Child Health 51 (2015) 608–613 © 2015 The Authors Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians)
AR Jones et al.
Referral patterns for paediatric bone density
Conclusion Multiple childhood diseases predispose to low bone density; however, paediatric bone densitometry is still underutilised and not appropriately supported by subsidies.
Acknowledgements The authors wish to acknowledge the extraordinary commitment of Ms Sue Kantor, the clinical densitometry technician for the 12 years encompassed by this study. These data are the direct result of her hard work and dedication to this patient group and the demonstration of the enduring legacy that Sue created for young people with bone health issues.
References 1 Australian Bureau of Statistics 2010. National Health Survey, Summary of Results, Australia 2007–2008 (Reissue), (cat no 4364.0 2009). Available from: http://www.abs.gov.au/ausstats/[email protected]/ Latestproducts/4364.0Main%20Features32007-2008%20(Reissue) ?opendocument&tabname=Summary&prodno=4364.0&issue=2007 –2008%20(Reissue)&num=&view= [accessed June 2013]. 2 Australian Institute of Health and Welfare, Rahman N, Bhatia K Impairments and disability associated with arthritis and osteoporosis. Arthritis series no. 4. Cat no. PHE 90. Canberra: AIHW, 2007 Available from: http://www.aihw.gov.au/WorkArea/DownloadAsset.aspx?id =6442459773 [accessed June 2013]. 3 Johnell O, Kanis JA. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos. Int. 2006; 17: 1726–33. 4 Cooper C. The crippling consequences of fractures and their impact on quality of life. Am. J. Med. 1997; 103 (2A): 12S–7S. 5 Hightower L. Osteoporosis: pediatric disease with geriatric consequences. Orthop. Nurs. 2000; 19: 59–62. 6 Bailey DA, McKay HA, Mirwald RL, Crocker PR, Faulkner RA. A six-year longitudinal study of the relationship of physical activity to bone mineral accrual in growing children: the University of Saskatchewan bone mineral accrual study. J. Bone Miner. Res. 1999; 14: 1672–9. 7 Hernandez CJ, Beaupre GS, Carter DR. A theoretical analysis of the relative influences of peak BMD, age-related bone loss and menopause on the development of osteoporosis. Osteoporosis Int. 2003; 14: 843–7. 8 Gordon CM, Leonard MB, Zemel BS. 2013 Pediatric Position Development Conference: executive summary and reflections. J. Clin. Densitom. 2014; 17: 219–24. 9 Bianchi ML. Osteoporosis in children and adolescents. Bone 2007; 41: 486–95. 10 Ward KA, Ashby RL, Roberts SA, Adams JE, Zulf Mughal M. UK reference data for the Hologic QDR Discovery dual-energy x ray
11 12
13
14
15
16
17 18
19
20
21 22 23
24
25
26
27
absorptiometry scanner in healthy children and young adults aged 6–17 years. Arch. Dis. Child. 2007; 92: 53–9. Seeman E. Pathogenesis of bone fragility in women and men. Lancet 2002; 359: 1841–50. French AR, Mason T, Nelson AM et al. Osteopenia in adults with a history of juvenile rheumatoid arthritis. A population based study. J. Rheumatol. 2002; 29: 1065–70. Finkelstein JS, Neer RM, Biller B, Crawford J, Kilbanski A. Osteopenia in men with a history of delayed puberty. N. Engl. J. Med. 1992; 326: 600–4. Hartman D, Crisp A, Rooney B, Rackow C, Atkinson R, Patel S. Bone density of women who have recovered from anorexia nervosa. Int. J. Eat. Disord. 2000; 28: 107–12. Herzog W, Minnie H, Deter C et al. Outcome of bone mineral density in anorexia nervosa patients 11.7 years after first admission. J. Bone Miner. Res. 1993; 8: 597–605. Ebeling PR, Daly RM, Kerr DA, Kimlin MG. Building healthy bones throughout life: an evidence-informed strategy to prevent osteoporosis in Australia. MJA Open 2013; 2 (Suppl. 1): 1–9. Backrach LK, Ward LM. Clinical review: bisphosphonate use in childhood osteoporosis. J. Clin. Endocrinol. Metab. 2009; 94: 400–9. Mergler S, Evenhuis HM, Boot AM et al. Epidemiology of low bone mineral density and fractures in children with severe cerebral palsy: a systematic review. Dev. Med. Child Neurol. 2009; 51: 773–8. Larson CM, Henderson RC. Bone mineral density and fractures in boys with Duchenne muscular dystrophy. J. Pediatr. Orthop. 2000; 20: 71–4. Wren TA, Lee DC, Kay RM, Dorey FJ, Gilsanz V. Bone density and size in ambulatory children with cerebral palsy. Dev. Med. Child Neurol. 2011; 53: 137–41. Rosen DS. Identification and management of eating disorders in children and adolescents. Pediatrics 2010; 126: 1240–53. Barnes C, Newall F, Ignjatovic V et al. Reduced bone density in children on long-term warfarin. Pediatr. Res. 2005; 57: 578–81. Harel Z, Johnson CC, Gold MA et al. Recovery of bone mineral density in adolescents following the use of depot medroxyprogesterone acetate contraceptive injections. Contraception 2010; 81: 281–91. Lee RH, Lyles KW, Colon-Emeric C. A review of the effect of anticonvulstant medications on bone mineral density and fracture risk. Am. J. Geriatr. Pharmacother. 2010; 8: 34–46. Henderson RC. The correlation between dual-energy X-ray absorptiometry measures of bone density in the proximal femur and lumbar spine of children. Skeletal Radiol. 1997; 26: 544–7. Hough JP, Boyd RN, Keating JL. Systematic review of interventions for low bone mineral density in children with cerebral palsy. Pediatrics 2010; 125: e670–8. Henderson RC, Lark RK, Newman JE et al. Pediatric reference data for dual X-ray absorptiometric measures of normal bone density in the distal femur. AJR Am. J. Roentgenol. 2002; 178: 439–43.
Journal of Paediatrics and Child Health 51 (2015) 608–613 © 2015 The Authors Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians)
613
doi:10.1111/jpc.12789
ORIGINAL ARTICLE
Bone density assessment in a tertiary paediatric centre over 13 years: Referral patterns and limitations Alicia R Jones,1,2 Margaret R Zacharin,2,3 Fergus J Cameron2,3 and Peter J Simm2,3 1
The Alfred Hospital, 2Department of Endocrinology and Diabetes, Royal Children’s Hospital, and 3Centre for Hormone Research, Murdoch Children’s Research Institute, Melbourne, Victoria, Australia
Aim: This study aims to examine the referral practices for the Royal Children’s Hospital (RCH) bone density service over the past 13 years and to demonstrate referral patterns and possible limitations to accessing paediatric bone densitometry. Methods: All patients attending the RCH Healthy Bones Unit for bone densitometry from 1 July 1999 to 30 June 2012, aged under 18 years of age, were included. Densitometry results were downloaded directly from the Hologic scanner into an Excel document. However, the referring unit and indication for referral were collected manually from either the referral card or the hospital’s scanned medical records system. Results: A total of 5767 bone densitometry scans were performed over the study period on 3004 patients. The majority of referrals were made by the Endocrinology department, followed by Adolescent Medicine, Gastroenterology and Neurology. Relatively few referrals were made by general paediatrics. The most common indication for bone density test overall was eating disorders, followed by steroid use, osteogenesis imperfecta and other collagen disorders and inflammatory bowel disease. The lowest lumbar spine z-scores by indication were for cerebral palsy and other causes of immobility. Conclusions: Multiple childhood diseases predispose to low bone density; however, paediatric bone densitometry is still underutilised and not appropriately supported by subsidies. Key words:
DXA; paediatrics bone density; skeletal fragility.
What is already known about this topic
What this paper adds
1 Osteoporosis is a leading cause of morbidity within Australia. 2 Failure to achieve peak bone mass in childhood predisposes to later osteoporosis. 3 Disorders of childhood such as cerebral palsy, chronic immobility, eating disorders, osteogenesis imperfecta and steroid use can cause low bone density and fragility fractures with high concurrent morbidity.
1 Many paediatric indications for bone densitometry are not covered by current Medicare subsidies. 2 Awareness of bone health issues is still variable even in a tertiary setting. 3 Patients with immobility have the lowest bone densities across all indications for scanning but are not recognised by the Medicare system as an indication for scanning.
Osteoporosis is a leading cause of morbidity within Australia, affecting an estimated 3% of the overall population.1 Osteoporosis in adulthood predisposes to fracture, increased disability and reduced quality of life.2–4 Rates of osteoporosis increase with age; however, it has been described as a ‘Paediatric disease with geriatric consequences’.5 This is because over 90% of peak bone mass is accrued by the age of 18,6 and failure to achieve an adequate peak bone mass during adolescence has been linked with later development of Correspondence: Dr Alicia Jones, Department of Endocrinology and Diabetes, Royal Children’s Hospital, 50 Flemington Road, Parkville VIC 3052 Australia. Fax: (03) 9345 6240; email: [email protected] Conflict of interest: The authors declare they have no conflicts of interest in relation to this manuscript Research carried out at The Royal Children’s Hospital, 50 Flemington Road, Parkville, 3052 Accepted for publication 21 October 2014.
608
osteoporosis.7 Unfortunately, the prevalence of impaired bone mass accrual in children is poorly understood. Osteoporosis in childhood is classified as primary or secondary (see Table 1).9 The International Society for Clinical Densitometry (ISCD) states that osteoporosis should not be diagnosed in children on the basis of low bone densitometry alone. Rather, the combination of low bone mineral density (BMD; z-score ≤ −2.0) and a clinically significant fracture allows this diagnosis to be reached.8 Furthermore, interpretation of densitometric data in paediatrics is difficult as the ‘normal’ BMD value changes with age, pubertal status and body size. However, dual-energy X-ray absorptiometry (DXA) remains the gold standard for assessing bone density in childhood, with a welldescribed correlation between DXA findings and fracture risk.9 The Royal Children’s Hospital (RCH) Healthy Bones Unit has been performing DXA scans since 1999 and is the main paediatric bone density service in Victoria. The ISCD has published guidelines on the indications and frequency of densitometry
Journal of Paediatrics and Child Health 51 (2015) 608–613 © 2015 The Authors Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians)
AR Jones et al.
Referral patterns for paediatric bone density
Table 1 Causes of osteoporosis in children and adolescents (adapted from ISCD guidelines8) Primary causes
Secondary causes
Osteogenesis imperfecta Idiopathic juvenile osteoporosis Ehler–Danlos syndrome Marfan syndrome
Immobility Cerebral palsy Duchenne muscular dystrophy Paraplegia Chronic inflammatory diseases Inflammatory bowel disease Cystic fibrosis Nutritional Vitamin D deficiency/rickets Malabsorption Coeliac disease Hypogonadism Eating disorders Endocrine disturbances Chronic liver disease Chronic renal disease Drug-related: glucocorticoids, warfarin, anticonvulsant medications, chemotherapy
testing8; however, the level of evidence for these recommendations varies, and as many indications are not supported by Medicare subsidies, it is likely that the service is underutilised. The aim of this study was to examine the referral practices for the RCH bone density service over the past 13 years, in order to define which departments refer, for which indications, and trends over time. It is hoped this will help to identify boundaries to optimal utilisation of DXA in paediatric medicine.
Fig. 1 Number of DXA scans by year. , total densitometry scans performed, number per year; , new referrals, number per year.
of birth, gender, scan date and age/weight/height at time of scan, and DXA results. Adjusting for height is performed after Ward et al. if in the appropriate age and height range for these reference data, whereas bone age adjustment is also undertaken if feasible.10 The referrer and indication for referral were extracted manually directly from each referral card, or where information on the referral was missing from the hospital’s scanned medical records system.
Statistical analysis Data were processed using Microsoft Excel for Mac 2008, version 12.3.6. Data were described as mean and range for both raw data and percentages, grouped initially by year then as a total of the entire study period.
Results Methods Setting The study was carried out at The RCH in Melbourne, a tertiary paediatric hospital that is the main centre for paediatric bone density testing in the state of Victoria. The RCH Healthy Bones Unit has been performing DXA scans since July 1999, using an Hologic QDR 4500 scanner (Hologic Inc., Bedford, MA, USA).
Participants All patients attending the RCH Healthy Bones Unit for DXA scans from July 1, 1999 to June 30, 2012 were included. Patients who were aged >18 years at time of scan were excluded, as were all those referred for DXA purely for research purposes (Hologic Inc., Bedford, MA, USA).
Data collection All DXA tests performed between the dates above were downloaded from the Hologic scanner and converted directly into an Excel document. Data included were the patient ID, name, date
A total of 5767 bone densitometry scans were performed over the study period on 3004 patients. The total number of referrals and new referrals by year were depicted in Figure 1. Although the total number of referrals increased over the study period, the number of new referrals remained relatively stable from 2000 to 2012. The endocrinology unit made the majority of referrals (2545, 44.1% of all referrals) over the entire study period and each year (see Fig. 2). However, the percentage of referrals each year made by endocrinology declined. There was an increase in the percentage of referrals from adolescent medicine (2.8% in 1999–2000, 15.2% in 2011–2012), haematology (0.5% in 1999–2000, 11.3% in 2011–2012) and neurology (0.9% in 1999–2000, 8.3% in 2011–2012) as a total of all referrals over the study period; however, referrals from the general paediatrics and other departments remained relatively stable over time. The most common indication for bone density test overall was eating disorders (743 referrals), followed by steroid use (670 referrals), osteogenesis imperfecta and other collagen disorders (614 referrals), and inflammatory bowel disease (531 referrals) (see Fig. 3). Over time, there was an increase in the percentage of referrals made for eating disorders, immobility (other) and
Journal of Paediatrics and Child Health 51 (2015) 608–613 © 2015 The Authors Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians)
609
Referral patterns for paediatric bone density
Fig. 2
AR Jones et al.
Referrals by unit. No legend; raw numbers of referrals per year by unit.
warfarin. There was a decrease in referrals for steroid use, hypogonadism and cystic fibrosis. Data were unable to be obtained for 15 referring units and 69 indications. The average lumbar spine z-score for the primary indications is depicted in Table 2. The lowest average z-score was for cerebral palsy (z –2.4), followed by immobility due to paraplegia and immobility due to other causes. The number of patients receiving a repeat DXA scan, interval between scans and number of scans per patient for the main indications is listed in Table 3.
Discussion To our knowledge, this is the largest audit of paediatric bone density testing. It highlights a number of complex issues in paediatric bone mass assessment. Although other options for assessing bone mass and strength exist such as peripheral quantitative computerised tomography, DXA scanning is still the most widely available modality with the best paediatric reference data and correlations with fracture risk.8,9 This modality has been used at The RCH since 1999. Over 90% of peak bone mass is achieved during childhood and adolescence. Appendicular longitudinal bone growth is rapid after birth and accelerates until puberty when appendicular bone growth slows and axial growth accelerates. Exposure to risk factors before and during puberty negatively affects this growth, resulting in a lower peak cortical thickness. This predisposes to lower adult BMD.11 Indeed, several studies have linked childhood disease with lower bone density in adulthood. French et al. studied 32 adult patients with a history of juvenile chronic arthritis before the age of 16 years and found 610
that a substantial proportion were osteopenic.12 Similarly, Finkelstein et al. studied 23 adult men with a history of delayed puberty and found that compared with controls they had significantly reduced bone density.13 Longitudinal studies of patients with eating disorders demonstrate long-term reductions in bone density 10–20 years following recovery.14,15 Osteoporosis was estimated to cost the Australian healthcare system $1.9 billion per year in direct costs and an additional $5.6 billion in indirect costs in the year 2000–2001.16 Prevention of osteoporosis, starting in childhood and focusing on optimising bone accrual rather than just reacting to losses later in life should thus be a high public health priority. Unfortunately, there are multiple barriers to diagnosing low bone density in paediatrics, and the service is relatively underutilised and children remain undiagnosed and untreated. These barriers include low referral rates, poor knowledge among medical professionals of interpretation of data, optimal timing of follow-up scans and the cost of bone densitometry, which in Australia is only subsidised if the indication meets one of five criteria specific by Medicare (see Table 4). Another difficulty in managing paediatric low bone density is how a clinician should respond to a low DXA result. Although there is good evidence for use of bisphosphonate therapy in adults, there is a lack of long-term data on the efficacy and safety of bisphosphonates in children and adolescents.17 As such if a BMD is found to be low/falling, a clinician needs to explore issues such as fracture history, immobility, diet and other preventative strategies, before considering bisphosphonate therapy. This study did not examine bisphosphonate use or the relation of this to BMD results. Cerebral palsy and chronic immobility are well-established causes of low BMD, with greater levels of immobility associated
Journal of Paediatrics and Child Health 51 (2015) 608–613 © 2015 The Authors Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians)
AR Jones et al.
Fig. 3
Referral patterns for paediatric bone density
Referrals by indication. No legend; raw numbers of referrals per year by indication.
with higher risk of low bone density.18–20 Our study supports previous reports, with the lowest average z-scores for the indications of cerebral palsy, paraplegia and other causes of immobility. Despite this well-known link between immobility and low bone density, there is still no Medicare code of funding for bone density testing in cases of immobilisation. The closest indication funded by Medicare is for a fragility fracture. It would clearly be preferable to diagnose low bone density before a fracture has occurred, thus permitting appropriate management strategies to be introduced to improve BMD and reduce fracture risk where possible. Furthermore, decisions as to the type, timing and duration of interventions for low impact fractures in these patients are also determined by changes in BMD. Thus, sequential testing is often beneficial and relies on a baseline measure with which to compare. Eating disorders are also a well-established cause of low bone density. It is recommended that patients with an eating disorder
Table 2
Average lumbar spine z-score by indication
Indication
Average z-score (range)
Cerebral palsy Immobility – paraplegia Immobility – other Hypogonadism Eating disorder Osteogenesis imperfecta Medication – steroid Medication – warfarin Fracture Inflammatory bowel disease Cystic fibrosis
−2.4 (−6.0, 3.6) −1.90 (−6.8, 0.1) −1.8 (−5.8, 2.4) −1.0 (−7.0, 2.6) −0.8 (−4.9, 2.6) −0.9 (−6.2, 2.5) −1.1 (−4.7, 2.5) −1.2 (−3.5, 2.7) −1.2 (−5.6, 2.3) −1.2 (−4.4, 2.7) −1.2 (−4.4, 2.0)
Journal of Paediatrics and Child Health 51 (2015) 608–613 © 2015 The Authors Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians)
611
Referral patterns for paediatric bone density
AR Jones et al.
Table 3 Interval for repeat DXA scan by indication Indication
Patients with repeat scan, n (%)
Average interval for repeat scan, months
Number of scans per individual, median (range)
Cerebral palsy Hypogonadism Eating disorder Osteogenesis imperfecta Medication – glucocorticoids Medication – warfarin Inflammatory bowel disease Cystic fibrosis
58 (22.83) 64 (20.71) 63 (8.48) 89 (14.50) 149 (22.24) 92 (25.27) 119 (22.41) 95 (23.40)
17.29 21.09 15.40 13.30 19.69 21.30 16.45 22.77
2 (1–10) 1 (1–6) 1 (1–6) 4 (1–14) 1 (1–9) 2 (1–8) 1 (1–9) 2 (1–10)
Table 4 Medicare subsidised indications for bone densitometry Medicare code
Indication
12306
Confirmation or presumptive diagnosis of low bone mineral density made on the basis of one or more fractures occurring after minimal trauma, or monitoring of low bone density proven by densitometry at least 12 months prior Diagnosis and monitoring of bone loss associated with prolonged glucocorticoid therapy, excess glucocorticoid secretion, male hypogonadism, female hypogonadism lasting more than 6 months before age 45 Diagnosis and monitoring of bone loss associated with primary hyperparathyroidism, chronic liver disease, chronic renal disease, proven malabsorptive disorders, rheumatoid arthritis, thyroxine excess. Measurement 12 months following a significant change in therapy for established low bone mineral density or presumptive lone bone mineral density following a minimal trauma fracture Screening patients over 70 years of age
12312
12315
12321
12323
and associated amenorrhoea of 6–12 months duration have a bone densitometry,21 as hypogonadism and other factors negatively impact bone mass. In our study, it was reassuring to see that the number of referrals for eating disorder increased with time, as has the prevalence and awareness of eating disorders. Performing BMD testing in these patients while young enables introduction of interventions to increase bone mass, which may assist in attaining a normal peak bone mass, thus reducing the risk of later osteoporosis. Another significant risk factor for low bone density in children is medication use. Exogenous glucocorticoids are a known cause of osteoporosis; however, other medications such as warfarin,22 depo provera23 and anticonvulsants24 have also 612
been linked with low bone density. Although official guidelines are lacking, National and international groups such as Osteoporosis Australia and the National Osteoporosis Foundation recognise these medications as risk factors for osteoporosis, and it is recommended that children on these medications long-term have bone densitometry to detect, monitor and potentially treat low bone density. It is fitting then that in our study, the number of referrals for warfarin increased over the time period. However, the number of referrals for other medications remained very low, with a total of only 46 referrals over the entire study. Possible causes of this may be a lack of awareness of the adverse effects of these medications among health professionals and the lack of funding to subsidise scans for this indication. The ISCD states that the minimum interval for repeating a bone measurement to monitor treatment with a bone-active agent or disease process is 6 months.8 In our study, the average interval for a repeat scan was greater than this, with the shortest average interval of 13 months for osteogenesis imperfecta. Although many patients will not need a repeat scan in a shorter time frame, some children with actively growing bones, more rapidly developing disease and use of medications that alter bone mass may benefit from more regular densitometry. Again, funding issues limit the number of scans undertaken, as currently only one scan every 12 or 24 months is funded depending on the indication. Although this may be appropriate for adults with slowly progressing disease, it is less appropriate for children and not in line with international standards. There are several limitations to our study. Departmental referral numbers will skew data related to referring units. Furthermore, many complex patients may be seen in more than one department and may have more than one indication for bone densitometry. For example, many patients with inflammatory bowel disease are also on steroids. Thus, the unit and indication listed on the card may not encompass the whole picture of the patient. A further limitation is that we did not analyse femoral BMD. As per the ISCD 2013 official position statement, the hip is not a preferred measurement site in growing children due to variability in skeletal development.8 However, some studies have demonstrated that there is significant deviation between proximal femur and lumbar spine BMD measurements in paediatric patients.25,26 This could confer an increased lower limb fracture risk, which would not be identified without the use of femoral z-scores. In children with conditions such as cerebral palsy and muscular dystrophy, contractures and deformities make positioning for proximal hip DXA difficult, as such the femoral neck, total hip and other measures of proximal femur are less reliable.25 To overcome these difficulties, some authors have suggested using distal femur BMD measurements, which appear to have more accuracy than proximal femur, as a marker of increased fracture risk.26,27 Unfortunately, our institution does not measure distal femur BMD. Finally, the data for the indication for referral were missing for 69 patient events. Patient information is essential to the accurate interpretation of BMD testing. This demonstrates an important gap in referrer education and necessarily limits reporting and data interpretation, thus reducing information for the referring physician.
Journal of Paediatrics and Child Health 51 (2015) 608–613 © 2015 The Authors Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians)
AR Jones et al.
Referral patterns for paediatric bone density
Conclusion Multiple childhood diseases predispose to low bone density; however, paediatric bone densitometry is still underutilised and not appropriately supported by subsidies.
Acknowledgements The authors wish to acknowledge the extraordinary commitment of Ms Sue Kantor, the clinical densitometry technician for the 12 years encompassed by this study. These data are the direct result of her hard work and dedication to this patient group and the demonstration of the enduring legacy that Sue created for young people with bone health issues.
References 1 Australian Bureau of Statistics 2010. National Health Survey, Summary of Results, Australia 2007–2008 (Reissue), (cat no 4364.0 2009). Available from: http://www.abs.gov.au/ausstats/[email protected]/ Latestproducts/4364.0Main%20Features32007-2008%20(Reissue) ?opendocument&tabname=Summary&prodno=4364.0&issue=2007 –2008%20(Reissue)&num=&view= [accessed June 2013]. 2 Australian Institute of Health and Welfare, Rahman N, Bhatia K Impairments and disability associated with arthritis and osteoporosis. Arthritis series no. 4. Cat no. PHE 90. Canberra: AIHW, 2007 Available from: http://www.aihw.gov.au/WorkArea/DownloadAsset.aspx?id =6442459773 [accessed June 2013]. 3 Johnell O, Kanis JA. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos. Int. 2006; 17: 1726–33. 4 Cooper C. The crippling consequences of fractures and their impact on quality of life. Am. J. Med. 1997; 103 (2A): 12S–7S. 5 Hightower L. Osteoporosis: pediatric disease with geriatric consequences. Orthop. Nurs. 2000; 19: 59–62. 6 Bailey DA, McKay HA, Mirwald RL, Crocker PR, Faulkner RA. A six-year longitudinal study of the relationship of physical activity to bone mineral accrual in growing children: the University of Saskatchewan bone mineral accrual study. J. Bone Miner. Res. 1999; 14: 1672–9. 7 Hernandez CJ, Beaupre GS, Carter DR. A theoretical analysis of the relative influences of peak BMD, age-related bone loss and menopause on the development of osteoporosis. Osteoporosis Int. 2003; 14: 843–7. 8 Gordon CM, Leonard MB, Zemel BS. 2013 Pediatric Position Development Conference: executive summary and reflections. J. Clin. Densitom. 2014; 17: 219–24. 9 Bianchi ML. Osteoporosis in children and adolescents. Bone 2007; 41: 486–95. 10 Ward KA, Ashby RL, Roberts SA, Adams JE, Zulf Mughal M. UK reference data for the Hologic QDR Discovery dual-energy x ray
11 12
13
14
15
16
17 18
19
20
21 22 23
24
25
26
27
absorptiometry scanner in healthy children and young adults aged 6–17 years. Arch. Dis. Child. 2007; 92: 53–9. Seeman E. Pathogenesis of bone fragility in women and men. Lancet 2002; 359: 1841–50. French AR, Mason T, Nelson AM et al. Osteopenia in adults with a history of juvenile rheumatoid arthritis. A population based study. J. Rheumatol. 2002; 29: 1065–70. Finkelstein JS, Neer RM, Biller B, Crawford J, Kilbanski A. Osteopenia in men with a history of delayed puberty. N. Engl. J. Med. 1992; 326: 600–4. Hartman D, Crisp A, Rooney B, Rackow C, Atkinson R, Patel S. Bone density of women who have recovered from anorexia nervosa. Int. J. Eat. Disord. 2000; 28: 107–12. Herzog W, Minnie H, Deter C et al. Outcome of bone mineral density in anorexia nervosa patients 11.7 years after first admission. J. Bone Miner. Res. 1993; 8: 597–605. Ebeling PR, Daly RM, Kerr DA, Kimlin MG. Building healthy bones throughout life: an evidence-informed strategy to prevent osteoporosis in Australia. MJA Open 2013; 2 (Suppl. 1): 1–9. Backrach LK, Ward LM. Clinical review: bisphosphonate use in childhood osteoporosis. J. Clin. Endocrinol. Metab. 2009; 94: 400–9. Mergler S, Evenhuis HM, Boot AM et al. Epidemiology of low bone mineral density and fractures in children with severe cerebral palsy: a systematic review. Dev. Med. Child Neurol. 2009; 51: 773–8. Larson CM, Henderson RC. Bone mineral density and fractures in boys with Duchenne muscular dystrophy. J. Pediatr. Orthop. 2000; 20: 71–4. Wren TA, Lee DC, Kay RM, Dorey FJ, Gilsanz V. Bone density and size in ambulatory children with cerebral palsy. Dev. Med. Child Neurol. 2011; 53: 137–41. Rosen DS. Identification and management of eating disorders in children and adolescents. Pediatrics 2010; 126: 1240–53. Barnes C, Newall F, Ignjatovic V et al. Reduced bone density in children on long-term warfarin. Pediatr. Res. 2005; 57: 578–81. Harel Z, Johnson CC, Gold MA et al. Recovery of bone mineral density in adolescents following the use of depot medroxyprogesterone acetate contraceptive injections. Contraception 2010; 81: 281–91. Lee RH, Lyles KW, Colon-Emeric C. A review of the effect of anticonvulstant medications on bone mineral density and fracture risk. Am. J. Geriatr. Pharmacother. 2010; 8: 34–46. Henderson RC. The correlation between dual-energy X-ray absorptiometry measures of bone density in the proximal femur and lumbar spine of children. Skeletal Radiol. 1997; 26: 544–7. Hough JP, Boyd RN, Keating JL. Systematic review of interventions for low bone mineral density in children with cerebral palsy. Pediatrics 2010; 125: e670–8. Henderson RC, Lark RK, Newman JE et al. Pediatric reference data for dual X-ray absorptiometric measures of normal bone density in the distal femur. AJR Am. J. Roentgenol. 2002; 178: 439–43.
Journal of Paediatrics and Child Health 51 (2015) 608–613 © 2015 The Authors Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians)
613
