The Journal of Bone & Joint Surgery

The Journal of Bone & Joint Surgery, Volume 88, Issue 6

Articles | June 01, 2006

Functional Significance of Bone Density Measurements in Children with Osteogenesis Imperfecta

Robert P. Huang, MD¹; Catherine G. Ambrose, PhD²; Elroy Sullivan, PhD¹; Richard J. Haynes, MD¹

¹ Shriners Hospital for Children-Houston, 6977 Main Street, Houston, TX 77030-3701. E-mail address for R.P. Huang: rhuang@shrinenet.org
² Department of Orthopaedics, University of Texas Health Science Center-Houston, 6431 Fannin, Suite 6148, Houston, TX 77030

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The authors did not receive grants or outside funding in support of their research for or preparation of this manuscript. They did not receive payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.

Investigation performed at Shriners Hospital for Children-Houston and University of Texas Health Science Center-Houston, Houston, Texas

The Journal of Bone and Joint Surgery, Incorporated

J Bone Joint Surg Am, 2006 Jun 01;88(6):1324-1330. doi: 10.2106/JBJS.E.00333

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Abstract

Background: The treatment of osteogenesis imperfecta has been directed at improvement of bone mineral density, yet the importance of bone mineral density in predicting functional and clinical outcome in this patient population has not been demonstrated. We used a validated functional outcome measure to identify the relationship between bone mineral density and physical function in children with osteogenesis imperfecta, and we also evaluated the relationship of bone mineral density to the rate of surgery and fracture in patients with osteogenesis imperfecta.

Methods: Twenty patients (age range, four to seventeen years) with osteogenesis imperfecta who had undergone bone mineral densitometry as measured by dual x-ray absorptiometry of the lumbar spine, wrist, and proximal aspect of the femur between November 1999 and April 2001 were retrospectively analyzed. Functional outcome was measured with use of the Pediatric Outcomes Data Collection Instrument. These questionnaires were completed by the parents of all twenty patients and, in addition, by fifteen patients in the study who were between the ages of eleven and eighteen years. Fracture and surgery rates were calculated on the basis of the number of documented fractures and surgical procedures that the patient had had from the time of the initial presentation until the time of the latest follow-up visit.

Results: There were significant relationships between the bone mineral density of the lumbar spine and the scores obtained on the parent-completed questionnaires with regard to upper-extremity functioning (r = 0.57, p < 0.01), transfers and basic mobility (r = 0.55, p = 0.01), sports and physical functioning (r = 0.55, p = 0.01), and global functioning (r = 0.60, p < 0.004). There were also significant relationships between the bone mineral density of the wrist and the scores obtained on the child-completed questionnaires with regard to upper-extremity functioning (r = 0.82, p < 0.01), sports and physical functioning (r = 0.76, p < 0.01), and global functioning (r = 0.83, p = 0.001). There were significant negative relationships between the bone mineral density of the lumbar spine and the rate of fractures (r = -0.69, p < 0.001) and the bone mineral density of the lumbar spine and the rate of surgery (r = -0.60, p < 0.01).

Conclusions: There is a relationship between bone mineral density and the functional outcome, rate of fracture, and rate of surgery in patients with osteogenesis imperfecta. Bone mineral density appears to be an indicator of disease severity and may be predictive of long-term functional outcome. To establish specific guidelines for treatment, more data on normative bone-mineral density in children with osteogenesis imperfecta will be needed.

Level of Evidence: Prognostic Level II. See Instructions to Authors for a complete description of levels of evidence.

Figures in this Article

Osteogenesis imperfecta is a connective-tissue disorder that is caused by mutations of the type-I collagen gene. These mutations cause quantitative and qualitative defects of type-I collagen fibers, resulting in major clinical manifestations of osteogenesis imperfecta, such as osteopenia, skeletal fragility, and progressive skeletal deformities. Depending on the severity of the disease, children with osteogenesis imperfecta may have delayed neuromotor development and substantial functional impairment in association with progressive skeletal deformities¹. Traditional assessment of the severity of osteogenesis imperfecta has been based on the history of fractures, the radiographic appearance, and the classification according to the system of Sillence et al.². The Sillence classification has been shown to correlate with range of motion, muscular strength, and ambulatory potential³. Unfortunately, the clinical usefulness of the Sillence classification has been hampered by the lack of a precise definition of osteogenesis imperfecta as well as the wide spectrum of variability in its clinical presentation⁴. The Sillence classification has not been found to correlate significantly with physical function or social function of children who are <7.5 years of age and does not have true prognostic value in predicting functional outcome⁵.

Because quantitative and qualitative defects in type-I collagen interfere with normal bone mineralization, the assessment of bone mineral density with use of dual x-ray absorptiometry may be a valuable diagnostic gauge of the clinical severity of osteogenesis imperfecta in children. To our knowledge, there are currently no guidelines for the assessment of bone mineral density or the interpretation of density data in children with osteogenesis imperfecta. Unlike postmenopausal osteoporosis, for which specific treatment guidelines based on dual x-ray absorptiometry measurements have been useful in clinical decision-making⁶, osteogenesis imperfecta has not been treated on the basis of information derived from dual x-ray absorptiometry. Studies of bone mineral density in patients with osteogenesis imperfecta have been limited by small sample sizes and the inclusion of subjects with only the mildest or the most severe forms of osteogenesis imperfecta. We also lack fundamental knowledge regarding the natural history of the disease and the risk factors associated with fracture morbidity in osteogenesis imperfecta.

The purpose of this study was to determine the prognostic value of bone-mineral-density measurements in growing children with osteogenesis imperfecta by comparing functional outcome with bone mineral density. In addition, we compared the rates of fracture and surgical procedures with the data regarding bone mineral density to further delineate the importance of bone-mineral-density assessment.

Materials and Methods

Materials and Methods | Results | Discussion | References

We reviewed the medical records of twenty-nine consecutive patients with osteogenesis imperfecta who had undergone bone-mineral-density assessment with use of dual x-ray absorptiometry between November 1999 and April 2001. Bone mineral density was assessed at the lumbar spine, the proximal aspect of the femur, and the wrist. In some patients, an intramedullary rod in the femur precluded dual x-ray absorptiometry scanning of the proximal aspect of the femur, but scans of the lumbar spine and/or wrist were obtained. Demographic information, such as age, gender, height, race, and weight, were recorded. Clinical information was also recorded, including ambulatory status, Sillence classification², scleral color, medical treatment, surgical treatment, and total duration of care from the date of the initial presentation to the date of the last visit prior to the institution of a pamidronate treatment protocol. None of the patients in the study had been treated with any bisphosphonate prior to or during this period. The medical records were specifically reviewed for documentation of fractures and surgical procedures as well as any associated medical conditions. A concomitant diagnosis of scoliosis, fracture, or nonunion did not exclude the patient from the study.

Functional outcome was measured with use of the Pediatric Outcomes Data Collection Instrument (PODCI) developed by the Pediatric Orthopaedic Society of North America. The PODCI questionnaire contains 114 questions from which four functional assessment and global functioning scores are derived. The functional assessment and global functioning scores have been shown to be valid for assessing function in children with moderate to severe musculoskeletal morbidity^7,8. The four functional assessment scores derived from the PODCI questionnaire are upper-extremity functioning, transfers and basic mobility, sports and physical functioning, and comfort and/or pain. The global functioning score is the average of these four functional assessment scores. The same questionnaire was administered directly to all patients between the ages of eleven and eighteen years and to all of the parents; thus, PODCI information was available from both the parents and the older children. Patients were excluded from the study if they did not have a completed functional outcome questionnaire.

Of the twenty-nine patients with osteogenesis imperfecta who underwent dual x-ray absorptiometry scanning, twenty had PODCI questionnaires completed by the parent. The other nine patients were excluded from the study. Of the twenty patients who had a PODCI questionnaire completed by the parent, fifteen were also old enough to complete the PODCI questionnaire themselves. All twenty patients had a dual x-ray absorptiometry scan of the lumbar spine, sixteen had a dual x-ray absorptiometry scan of the wrist, and eight had a dual x-ray absorptiometry scan of the proximal aspect of the femur. Of the fifteen patients who completed the questionnaire, all had a dual x-ray absorptiometry scan of the lumbar spine, eleven had a dual x-ray absorptiometry scan of the wrist, and six had a dual x-ray absorptiometry scan of the proximal aspect of the femur.

Statistical calculations were performed with the use of JMP IN 5.1 software (SAS Institute, Cary, North Carolina). Statistical calculations for all patients who had a PODCI questionnaire completed by a parent were performed separately from those for the subset of fifteen patients who completed the PODCI questionnaire themselves. Descriptive parameters, such as age, body mass index, height, weight, and duration of follow-up (from the date of the initial presentation until the date of the dual x-ray absorptiometry scan), were calculated. The rates of fracture and surgery were then calculated on the basis of the duration of follow-up and the number of documented fractures and surgical procedures identified. One-way analysis of variance was used to compare the relationships of continuous parameters, including body mass index, bone mineral density, and individual PODCI domains, with respect to gender. The Pearson correlation coefficient was used to perform an initial analysis comparing body mass index, bone mineral density, and individual PODCI domains by age. Statistical analysis of the individual PODCI domain data, rate of fracture, and rate of surgery in relationship to bone mineral density was performed with use of the Pearson correlation. P values of =0.05 were considered significant. This study was approved by the Committee for the Protection of Human Subjects at the University of Texas Health Sciences Center at Houston.

Results

Materials and Methods | Results | Discussion | References

The patients included in the study varied widely with regard to type of osteogenesis imperfecta. Five patients had type-I, seven patients had type-III, and eight patients had type-IV osteogenesis imperfecta. The ages of the patients ranged from four to seventeen years. The average age (and standard deviation) of all twenty patients with a PODCI questionnaire completed by the parent was 10.6 ± 3.4 years. These children had a mean body mass index of 22.9 ± 7.8 kg/m² and an average duration of care of 9.3 ± 4.0 years. The average age of the fifteen patients who completed the PODCI questionnaire themselves was 11.7 ± 3.0 years. These children had a mean body mass index of 24.0 ± 8.5 kg/m² and an average duration of care of 9.7 ± 4.1 years.

The average rate of surgery was 0.48 ± 0.4 times per year in all twenty patients and 0.46 ± 3 times per year in the subset of fifteen patients who completed the PODCI questionnaire themselves. The average rate of fractures was 0.82 ± 0.6 per year in all twenty patients and 0.81 ± 0.54 per year in the fifteen patients who completed the PODCI questionnaire themselves. With the numbers available, age and gender were not significantly correlated to body mass index; bone mineral density in the lumbar spine, femur, or wrist; or any of the PODCI functional domains.

The correlation matrices of bone mineral density in the lumbar spine, femur, and wrist and their relationship to the upper-extremity-functioning, transfers-and-basic-mobility, and sports-and-physical-functioning domains of the parent-completed and child-completed PODCI questionnaires are summarized in Tables I and II. Evaluation of the parent-completed PODCI questionnaire scores revealed significant relationships between bone mineral density of the lumbar spine and upper-extremity functioning (r = 0.57, p < 0.01), transfers and basic mobility (r = 0.55, p = 0.01), sports and physical functioning (r = 0.55, p = 0.01), and global functioning (r = 0.60, p < 0.004). Evaluation of the child-completed PODCI questionnaire scores revealed significant relationships between bone mineral density in the wrist and upper-extremity functioning (r = 0.82, p < 0.01), transfers and basic mobility (r = 0.76, p < 0.01), sports and physical functioning (r = 0.76, p < 0.01), and global functioning (r = 0.83, p = 0.001). Figure 1 illustrates the significant positive correlation between bone mineral density in the lumbar spine and upper-extremity function as measured by the parent-completed PODCI questionnaires for all twenty patients. Overall, the functional outcome appeared to improve with increasing bone mineral density in the lumbar spine and wrist. Interestingly, with the numbers studied, the comfort and/or pain and happiness domains of both the parent-completed and child-completed PODCI questionnaires were not found to have any correlation with bone mineral density at the lumbar spine, wrist, or proximal aspect of the femur.

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TABLE I Correlations of Body Mass Index and Bone Mineral Density with Domains of Parent-Completed PODCI Questionnaire^*

		Bone Mineral Density
PODCI Domain	Body Mass Index	Lumbar Spine	Wrist	Femur
Upper-extremity functioning	NS	0.57†	NS	NS
Transfers and basic mobility	—0.66†	0.55‡	0.51§	NS
Sports and physical functioning	—0.49§	0.55‡	NS	0.73§

PODCI = Pediatric Outcomes Data Collection Instrument, and NS = not significantp < 0.01p = 0.01p < 0.05

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TABLE I Correlations of Body Mass Index and Bone Mineral Density with Domains of Parent-Completed PODCI Questionnaire^*

		Bone Mineral Density
PODCI Domain	Body Mass Index	Lumbar Spine	Wrist	Femur
Upper-extremity functioning	NS	0.57†	NS	NS
Transfers and basic mobility	—0.66†	0.55‡	0.51§	NS
Sports and physical functioning	—0.49§	0.55‡	NS	0.73§

PODCI = Pediatric Outcomes Data Collection Instrument, and NS = not significantp < 0.01p = 0.01p < 0.05

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TABLE II Correlations of Body Mass Index and Bone Mineral Density with Domains of Child-Completed PODCI Questionnaire^*

		Bone Mineral Density
PODCI Domain	Body Mass Index	Lumbar Spine	Wrist	Femur
Upper-extremity functioning	NS	0.56†	0.82‡	NS
Transfers and basic mobility	—0.59†	NS	0.76‡	NS
Sports and physical functioning	—0.60†	NS	0.76‡	0.86†

PODCI = Pediatric Outcomes Data Collection Instrument, and NS = not significantp < 0.05p < 0.01

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TABLE II Correlations of Body Mass Index and Bone Mineral Density with Domains of Child-Completed PODCI Questionnaire^*

		Bone Mineral Density
PODCI Domain	Body Mass Index	Lumbar Spine	Wrist	Femur
Upper-extremity functioning	NS	0.56†	0.82‡	NS
Transfers and basic mobility	—0.59†	NS	0.76‡	NS
Sports and physical functioning	—0.60†	NS	0.76‡	0.86†

PODCI = Pediatric Outcomes Data Collection Instrument, and NS = not significantp < 0.05p < 0.01

The correlation matrices of the bone mineral density of the lumbar spine, femur, and wrist in relation to the rate of fractures and surgical procedures per year are listed in Table III. A significant association was found between the bone mineral density of the lumbar spine and the annual rate of fractures (r = -0.69, p < 0.001) as well as the annual rate of surgical procedures (r = -0.60, p < 0.01). Figures 2 and 3 demonstrate the negative correlation of bone mineral density in the lumbar spine with the rates of fractures (Fig. 2) and surgical procedures (Fig. 3). As the bone mineral density of the lumbar spine increased, the frequencies of fractures and surgical procedures decreased. With the numbers studied, the comfort and/or pain and happiness domains of both the parent-completed and child-completed PODCI questionnaires did not show any relationship with the rate of fracture or the rate of surgery.

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TABLE III Correlations of Bone Mineral Density with Fractures and Surgical Procedures^*

	Bone Mineral Density
	Lumbar Spine	Wrist	Femur
Fractures per year	—0.69†	NS	—0.82‡
Surgical procedures per year	—0.60§	NS	NS

NS = not significantp < 0.001p = 0.01p < 0.01

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TABLE III Correlations of Bone Mineral Density with Fractures and Surgical Procedures^*

	Bone Mineral Density
	Lumbar Spine	Wrist	Femur
Fractures per year	—0.69†	NS	—0.82‡
Surgical procedures per year	—0.60§	NS	NS

NS = not significantp < 0.001p = 0.01p < 0.01

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Fig. 1: Graph demonstrating the positive linear relationship of upper-extremity functioning with bone mineral density of the lumbar spine. As the bone mineral density of the lumbar spine increases, the upper-extremity score, as measured with the PODCI questionnaires completed by the parents, also increases. The solid line represents the linear fit of the Pearson correlation, and the dashed lines represent the 95% confidence interval. The linear equation, the r value squared, and the p value are also given.

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Fig. 2: Graph showing that the rate of fractures per year decreases as the bone mineral density of the lumbar spine increases. The solid line represents the linear fit of the Pearson correlation, and the dashed lines represent the 95% confidence interval.

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Fig. 3: Graph demonstrating that the rate of surgical procedures per year decreases with increasing bone mineral density of the lumbar spine. The solid line represents the linear fit of the Pearson correlation, and the dashed lines represent the 95% confidence interval.

Discussion

Materials and Methods | Results | Discussion | References

Dual x-ray absorptiometry is an excellent tool for screening and monitoring bone density because the cost is relatively low, the radiation exposure is low, and the technique is precise enough to be used in the long-term follow-up of patients. The results of clinical studies of osteoporosis in adults have demonstrated that low bone-mineral-density values are associated with an increased risk of fracture^9-11. For example, the age-adjusted risk of hip fracture increases by 2.6 times with a decrease in femoral bone mineral density of one standard deviation¹¹. On the basis of the clinical associations between bone mineral density and fracture risk, the World Health Organization has developed clinical guidelines for the diagnosis and treatment of osteoporosis¹².

There have been several studies in the literature in which dual x-ray absorptiometry has been used to assess the bone mineral density of patients with osteogenesis imperfecta^13,14. Zionts et al.¹³ compared the bone mineral density of nine subjects with mild osteogenesis imperfecta with that of age and gender-matched control subjects. They concluded that the patients with osteogenesis imperfecta had significantly lower bone mineral density (p < 0.001) at the lumbar spine and the femoral neck than did the age and gender-matched controls, and they suggested that dual x-ray absorptiometry may be a useful screening tool to help determine which patients may need genetic testing for osteogenesis imperfecta. Cepollaro et al.¹⁴ found that bone mineral density at the lumbar spine and the distal part of the radius, as assessed with either dual x-ray absorptiometry or ultrasound density, in twenty-one patients with osteogenesis imperfecta was significantly different (p < 0.005) from that in age and gender-matched controls. Correlations were not performed to compare the measurements with clinical outcomes.

We are aware of only one study in the literature in which an attempt was made to correlate fracture incidence with dual x-ray absorptiometry assessments in untreated patients with osteogenesis imperfecta. Reinus et al.¹⁵ examined bone mineral density in the lumbar spine of twenty-seven patients with osteogenesis imperfecta and correlated the values to parameters of growth (age, height, and weight) and lifetime risk of fracture. Correlation values were relatively high for the growth parameters, ranging from 0.78 for body surface area to 0.74 for weight. The correlation of bone mineral density of the lumbar spine to lifetime fracture risk was -0.47. In this study, selected patients were also examined serially to determine how bone mineral density changed with age for this population. Reinus et al. determined that the spinal mineralization rate expressed as the yearly rate of change of the bone mineral density z-score was not significantly different from that of a normal pediatric population.

More recently, treatment with bisphosphonates to increase bone mineral density has been used to a greater extent in patients with osteogenesis imperfecta. Falk et al.¹⁶ described a series of six children with osteogenesis imperfecta who had an annual 48% increase in bone mineral density of the lumbar spine while receiving intravenous pamidronate therapy for a minimum of two years. Arikoski et al.¹⁷ reproduced these improvements in bone mineral density with the use of intravenous pamidronate therapy in twenty-six children with osteogenesis imperfecta, demonstrating a 48.7% increase in bone mineral density in the first year of treatment. This dramatic increase in bone mineral density is above and beyond what would be expected in association with the normal growth and age of the child¹⁸. This was further confirmed by Grissom et al.¹⁹, who, in their review of twenty children with osteogenesis imperfecta as well as eighteen children with spastic quadriplegia, reported that pamidronate was associated with a 78% increase in bone mineral density of the spine in the children with osteogenesis imperfecta over a twenty-eight-month period. In addition to increasing the bone mineral density in children with osteogenesis imperfecta, intravenous pamidronate therapy has also been shown to dramatically decrease bone turnover and reduce the levels of urine N-telopeptide and serum bone-specific alkaline phosphatase^17,20,21.

Despite these dramatic increases in bone mineral density and reduction in bone turnover, major questions remained regarding the clinical benefit of increasing bone mineral density and reducing bone turnover. Lee et al.²¹ investigated the efficacy and safety of cyclic administration of pamidronate in six children with osteogenesis imperfecta and discovered that increasing bone mineral density dramatically reduced the fracture rate to zero within a one-year time frame. Dimeglio et al.²⁰ found a 25% increase in mean annualized total body areal bone mineral density and a dramatic reduction in the rate of fractures (from eighty fractures in 111 months to twenty-five fractures in 152 months) after treatment with intravenous pamidronate. In a prospective randomized study of children with osteogenesis imperfecta treated with olpadronate for two years, Sakkers et al.²² reported a 31% reduction in the relative risk of fractures associated with increases in bone mineral density of the spine. In a large, three-year, randomized controlled study of sixty-four prepubertal children with osteogenesis imperfecta, Gatti et al.²³ found that intravenous neridronate, infused every three months, significantly increased bone mineral density by 18% to 25% per year (p < 0.005) in the spine and hips while decreasing the risk of fractures by a relative risk of 0.36.

While increasing bone mineral density has been shown to reduce the rate of fractures in children with osteogenesis imperfecta, a corresponding improvement in physical function has not been demonstrated. On the contrary, the results of studies by Letocha et al.²⁴ and Sakkers et al.²², who looked specifically at the functional outcome of treatment with pamidronate, do not support the notion that treatment with bisphosphonates improves overall function in children with osteogenesis imperfecta. Sakkers et al.²², who recruited thirty-four patients with osteogenesis imperfecta and randomly assigned them to olpadronate or placebo treatment over a two-year period, found that there were no detectable effects on functional outcome despite a reduction in the relative risk of fractures. Letocha et al.²⁴, who conducted a randomized controlled trial of eighteen children with osteogenesis imperfecta who were given intravenous pamidronate or placebo over a one-year period, found no short-term functional gains in the ability to walk or for growth despite improvements in bone mineral density.

The results of our study are consistent with the findings of Reinus et al.¹⁵, Dimeglio et al.²⁰, Lee et al.²¹, Sakkers et al.²², and Gatti et al.²³. We found that the annual fracture rate in our patient population was closely correlated with bone mineral density of the lumbar spine. Furthermore, the rate of surgery was inversely related to the bone mineral density of the lumbar spine; patients with greater bone mineral density of the lumbar spine, regardless of age or gender, underwent fewer procedures per year. This observation is consistent with the findings of Zacharin and Kanumakala²⁵, who, during a two-year observational study, noted a decrease in the rate of surgical procedures per patient. More importantly, with use of the PODCI instrument, we demonstrated a linear relationship between bone mineral density of the lumbar spine and functional outcomes.

Our results with regard to functional outcome contrast sharply with the results reported by Sakkers et al.²² and Letocha et al.²⁴. However, the study design and hypothesis of those studies differed appreciably from ours. In both of those studies, the authors examined differences between the treatment group and a control group; thus, there may have been undetected differences as a result of inadequate power. Furthermore, the duration of both studies was very short for the purpose of considering functional outcome. Our finding of a linear relationship between bone mineral density and functional outcome is consistent with the findings of Zacharin and Kanumakala²⁵ and Falk et al.¹⁶. Our results suggest that increases in bone mineral density may ultimately improve the functional outcome of children with osteogenesis imperfecta.

One major limitation of this study is that it included only twenty patients, which raises questions about its generalizability to the overall population of patients with osteogenesis imperfecta. However, it appears that we analyzed a reasonable sample of patients with osteogenesis imperfecta. There were no predetermined selection criteria, and the patients had major types of osteogenesis imperfecta with varying degrees of disease severity as classified with the system of Sillence et al.². It is important to note, however, that not all of our patients had reached skeletal maturity; thus, the results may not be applicable to the adult population of patients with osteogenesis imperfecta. The other major limitation of the study is that it is a retrospective, cross-sectional investigation. Although the study may be helpful in providing prognostic criteria, based on bone mineral density, with regard to the natural history of osteogenesis imperfecta, the true natural history can be ascertained only through a longitudinal, prospective study. A prognostic tool has been lacking in the clinical evaluation of patients with osteogenesis imperfecta. Dual x-ray absorptiometry assessment of bone mineral density appears to be a useful clinical tool in determining the severity of disease, the risk for future fractures, and the long-term functional outcome in patients with osteogenesis imperfecta. ?

References

Materials and Methods | Results | Discussion | References

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Sakkers R, Kok D, Engelbert R, van Dongen A, Jansen M, Pruijs H, Verbout A, Schweitzer D, Uiterwaal C. Skeletal effects and functional outcome with olpadronate in children with osteogenesis imperfecta: a 2-year randomised placebo-controlled study. Lancet. 2004;363: 1427-31.3631427 2004 [PubMed][CrossRef]

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Topics

osteogenesis imperfecta ; bone mineral density ; fracture ; femur ; lumbar vertebra ; wrist ; x-ray absorptiometry, dual-energy

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Robert P. Huang, Catherine G. Ambrose, Elroy Sullivan, Richard J. Haynes; Functional Significance of Bone Density Measurements in Children with Osteogenesis Imperfecta. The Journal of Bone & Joint Surgery. 2006 Jun;88(6):1324-1330.

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