Elsevier

Bone

Volume 113, August 2018, Pages 137-143
Bone

Full Length Article
A comparative study of quality of life, functional and bone outcomes in osteogenesis imperfecta with bisphosphonate therapy initiated in childhood or adulthood

https://doi.org/10.1016/j.bone.2018.05.021Get rights and content

Highlights

  • OI patients treated with early bisphosphonate treatment resulted in increased BMD and higher levels of physical activity.

  • Despite the physical burden associated with OI, quality of life and psychological wellbeing remain high.

  • Improvements in BMD with bisphosphonate treatment accompanied lower prepubertal fracture rate.

  • Results suggest early bisphosphonate treatment improves physical activity, particularly in less severe forms of OI.

Abstract

Bisphosphonates have been used for treatment of bone fragility disorders for over 25 years to increase bone mineral density (BMD). Anecdotally, bisphosphonate-treated Osteogenesis Imperfecta (OI) has a different trajectory to the natural history of untreated OI in terms of fracture incidence, quality of life and physical function, with minimal published evidence to support this clinical observation. This study describes functional outcomes of a cohort of adults with OI, stratified according to severity and treated with intravenous bisphosphonates as children. Reported outcomes included fracture incidence before and after puberty, mobility and BMD outcomes of this cohort. The cohort was compared to adults with OI who were never treated as children. All participants completed four questionnaires: a study specific questionnaire addressing fracture and treatment history, WHOQOL-BREF (quality of life), SF-36 (musculoskeletal function) and IPAQ (physical activity), and medical records were reviewed. Fifty-two adults with OI (80% response rate) completed the questionnaires; 33 of whom were treated with bisphosphonates in childhood. The childhood treated cohort had higher lumbar spine BMD than the adult treated cohort (z-score − 0.4 at mean age 21.3 years versus −2.1 at mean age 40.9 years; p = 0.003). Pre-pubertal fracture incidence was reduced for all severities of OI in the childhood treated cohort (less severe OI, p = 0.01; more severe OI, p < 0.001), but post-pubertal fracture incidence was higher for less severe OI (p < 0.001). In less severe OI, childhood treated individuals had higher levels of physical activity (p = 0.004) and physical functioning (p = 0.01) than adult treated individuals. Incidence of scoliosis was not different between cohorts. There were no differences in quality of life scores between the two cohorts. Improvements in BMD do not appear to influence the prevalence of scoliosis. Results suggest that treatment with bisphosphonates at an earlier age improves physical activity, particularly in less severe forms of OI but may not alter quality of life.

Introduction

Osteogenesis imperfecta (OI) is a heritable connective tissue disorder characterised by increased bone fragility and low bone mass, predominantly caused by mutations in either of the two genes encoding collagen type 1, COL1A1 or COL1A2, [1]. The incidence of OI has been estimated at 1 in 10,000 to 20,000 births [2,3]. It is not unusual for people with moderate-to-severe OI to have >100 fractures throughout their lifetime [4]. The impact that OI has on quality of life and social functioning cannot be underestimated. Historically people with severe OI have been non-ambulatory, suffered significant physical and social limitations, and died prematurely from disease-related complications (respiratory compromise, cardiac failure, neurological complications and by exacerbating accidents) [[5], [6], [7], [8]].

Bisphosphonate therapy has altered medical management of children with OI, with positive effects on bone histology, bone geometry and bone density Z scores [9,10] but currently there is no consensus on an optimum treatment regimen. Bisphosphonates are potent anti-resorptive agents that interfere with bone modelling and remodelling and have been used for over 30 years for treatment of secondary osteoporosis, most often related to corticosteroid use or in post-menopausal bone loss, where they have been shown to increase bone density and to decrease fracture rate [11].

For OI, bisphosphonates have been used over the past 20 years. Most current literature evaluating its use in OI is limited to short-term safety and efficacy. Evidence for reduction in fracture rate is lacking, although pain reduction and mobility are generally considered to improve [12,13]. There is ongoing debate as to whether bisphosphonates reduce the prevalence or progression of scoliosis or improve bone pain and functional mobility [14,15]. Furthermore, physical and psychological aspects of quality of life have also been described to be lower than population norms despite bisphosphonate treatment [16]. However, these findings are yet to be reproduced, with other studies suggesting compared to the average healthy population, only physical activity is poorer in OI with psychological well-being comparable [17].

Anecdotally, children with OI treated with bisphosphonates fare better in adulthood. However, there are few validated studies regarding long-term outcomes and whether outcomes have improved with bisphosphonate treatment. It is important to explore longitudinal outcomes to help guide management, assist with developing standardised treatment regimens and emphasise the benefits of current practice. This study describes the functional outcomes of a cohort of adults with OI treated with intravenous bisphosphonates as children, and explores fracture incidence, BMD outcomes and pain of this cohort compared with adults with OI who were never treated as children.

Section snippets

Study design

This is a cross-sectional survey.

Setting

The Royal Children's Hospital (RCH) Melbourne is a major specialist paediatric hospital in Victoria. Participants were recruited from February to August 2017 from RCH. Adult OI participants were recruited from the private rooms of an author (MZ).

Participants

Two cohorts of adults over age 18 years, all with a confirmed clinical and/or genetic diagnosis of OI participated in the study.

  • 1.

    Childhood treated cohort: Those who had received at least one infusion of bisphosphonate

Results

A total of 65 adults with OI were invited to participate in the study with 52 adults completing the questionnaires (80% response rate). Table 1 summarises the demographic data of participants. There were 33 adults in the childhood treated cohort and 19 adults in the adult treated cohort. The median age of the two cohorts was significantly different (24 years versus 40 years; p < 0.001). Those in the childhood treated cohort were more likely to be single (OR 29.0, 95% CI [5.6–149.7]; p < 0.01)

Discussion

This study is the first in Australia to document outcomes of OI in adulthood following bisphosphonate treatment in childhood, and to report that bisphosphonates resulted in ongoing accrual of bone mass during childhood and adolescence. This resulted in BMD at lumbar spine comparable with that of a normal population, as a surrogate measure of bone hardness and thus of future fracture risk. However, DXA data does not explore bone quality and bisphosphonates are not able to modify the underlying

Conclusion

This is the first study to describe outcomes of OI in adulthood after bisphosphonate treatment during childhood in Australia, demonstrating increased BMD in all treated cohorts and that early bisphosphonate treatment results in higher overall levels of physical activity, although limited by physical disability for more severe OI. Despite the physical burden associated with OI, quality of life and psychological wellbeing remain high. Improvements in BMD with bisphosphonate treatment had no

Acknowledgements

The study team would like to thank Ms. Julia McCombe for her administrative expertise, Ms. Lindy Tukavkin for her patience and perseverance with patient records (with patient recruitment), and the participants for all their contributions.

Funding sources

None.

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