Repair of osteopenia in children with juvenile rheumatoid arthritis

doi:10.1016/S0022-3476(06)80006-5

The Journal of Pediatrics

Volume 122, Issue 5, May 1993, Pages 693-696

https://doi.org/10.1016/S0022-3476(06)80006-5 Get rights and content

To test the hypothesis that the presence of osteopenia in juvenile rheumatoid arthritis is directly correlated with clinical disease activity and therefore reversible, we prospectively studied cortical bone mineral density (BMD) serially in 27 children. Twenty-four (89%) had BMD≥2 SD below age-related normal values (disease duration 49.3±7.7 months) at the beginning of the study. Of 27 children who had clinical disease improvement measured by a disease activity score during our study period, 17 (63%) had significant improvement or significant normalization, or both, of their BMD (0.34±0.13 gm/cm² at initiation and 0.41±0.17 gm/cm² at completion, p<0.05; disease activity score of 3.4±0.2 at initiation and 1.4±0.2 at completion, p<0.005). The increase in BMD was associated with a similar directional change in serum osteocalcin concentrations (4.6±1 ng/ml at initiation vs 9.1±1.1 ng/ml). The 10 patients whose disease became or remained active had a decreased or unchanged low serum osteocalcin level and BMD (BMD 0.37±0.17 gm/cm² at initiation and 0.37±0.16 gm/cm² at completion; disease activity score of 3.1±0.3 at initiation and 3.4±0.2 at study completion). We conclude that children with JRA who have improvement in their disease activity have an improvement in BMD heralded by an increase in serum osteocalcin values. (J Pediatr 1993; 122:693-6)

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Cited by (59)

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The systemic and focal joint inflammation that characterizes many of the rheumatologic disorders can also be accompanied by adverse effects on the skeleton. Much of the attention has focused on the focal bone resorption in articular and periarticular bone associated with disorders such as rheumatoid arthritis (RA), the prototypical inflammatory joint disease. However, it is clear that many of the inflammatory rheumatic disorders also have effects on systemic bone remodeling. Studies have documented that osteoporosis and increased risk of fracture account for a component of the morbidity associated with these conditions. In part, these adverse skeletal effects may be related to the therapies used to treat these diseases. This review will focus on the inflammatory rheumatologic disorders that target the articular and periarticular tissues. These entities include RA, juvenile idiopathic arthritis (previously classified as juvenile RA), the seronegative spondyloarthropathies, and systemic lupus erythematosus. It is important to note, however, that many of the related immune-mediated rheumatic conditions such as systemic vasculitis may also be accompanied by adverse effects on skeletal remodeling and increased risk for osteoporosis, in part, related to the use of high-dose glucocorticoids and other therapies that adversely affect the skeleton.
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The prevention and treatment of glucocorticoid-induced osteopaenia in juvenile rheumatic disease: A randomised double-blind controlled trial
2019, EClinicalMedicine
Citation Excerpt :
Steroids reduce peak bone mass and fracture risk increases as steroid dose increases [3,9,10]. Many more children receive recurrent courses of steroids for other common diseases such as asthma, with an associated increased risk of fracturing [11,12]. Children receiving steroids can, unlike adults, dramatically increase their BMD when their disease is brought under control [13].
Children and young people (CYP) with chronic rheumatic conditions; Juvenile Idiopathic Arthritis, Juvenile Systemic Lupus Erythematosus, Juvenile Dermatomyositis and Juvenile Vasculitis, treated with steroids, have low bone density, increased fracture risk and are likely to have suboptimal peak bone mass. There is currently no evidence base for the management of steroid-induced bone loss in children with rheumatic diseases.
We undertook a multi-centre double dummy double-blind randomised placebo controlled trial to investigate whether the bisphosphonate risedronate was superior to alfacalcidol or calcium and vitamin D supplementation in the prevention and treatment of steroid-induced osteopaenia in these children. Patients were stratified and randomised in a 1:1 ratio, into: placebo; alfacalcidol; risedronate. The primary outcome was the change in lumbar spine bone mineral density z score (LSaBMDz) measured by dual energy x-ray absorptiometry at one year. Secondary outcome was fracture rate.
Two hundred and seventeen patients were recruited to the study. Seventy seven placebo, 71 alfacalcidol, and 69 risedronate. Highly statistically significant differences were observed in the change in LSaBMDz between the placebo and risedronate groups; 0.274, 95% CI (0.061, 0.487) (p < 0.001) and between the risedronate and the alfacalcidol groups; 0.326 95% CI (0.109, 0.543) (p < 0.001). The difference observed between the alfacalcidol and placebo group was not statistically significant.
Highly statistically significant differences were seen in the change in Total Body Less Head aBMD-Z Score between the placebo and risedronate groups (p < 0.01) but not between the alfacalcidol and risedronate groups. No significant differences in fracture frequency, adverse or serious adverse reactions were observed between the groups.
Children and adolescents receiving steroids for rheumatic diseases benefit from prophylactic treatment with bisphosphonates to increase LSaBMD. Alfacalcidol is ineffective.
The impact of underlying disease on fracture risk and bone mineral density in children with rheumatic disorders: A review of current literature
2016, Seminars in Arthritis and Rheumatism
Citation Excerpt :
This is problematic in that it is likely not appropriate to group children with widely disparate disease and/or treatment durations, reducing the ability to identify relationships and differences between groups. Some authors have taken the important step of presenting longitudinal data [9,27,29,31,38,40,55–57,59–61,65,74,75,77,81,85,96]. Long-term, longitudinal follow-up will be needed to completely understand the impact of childhood inflammatory disease on the adult skeleton.
Childhood rheumatic diseases are associated with negative impacts on the skeleton, related to both the underlying illness and complications of therapy. The effects of medications like corticosteroids are well recognized, leading to reductions in bone mineral density and bone strength and concomitant increases in bone fragility and fracture risk. The impact of factors directly attributable to the underlying disease is not as well recognized. In this article, we review relevant literature to identify data which can contribute to an understanding of the impact of childhood rheumatic disease on the skeleton. We conclude that childhood rheumatic diseases are associated with reductions in bone mineral density and increased risk of vertebral and non-vertebral fractures. These data are strongest for juvenile arthritis, while conclusions are more limited for other rheumatic illnesses, like juvenile systemic lupus erythematosus or juvenile dermatomyositis, due to small numbers of patients studied. Finally, we make recommendations for areas in need of further research. These include the need for long-term longitudinal studies and for data to be collected in patients who have not been treated with corticosteroids.
Pharmacology and Drug Therapy: Nonbiologic Therapies
2015, Textbook of Pediatric Rheumatology
Osteoporosis Associated with Rheumatologic Disorders
2013, Osteoporosis: Fourth Edition
The systemic and focal joint inflammation that characterizes many of the rheumatologic disorders is frequently accompanied by adverse effects on the skeleton. Much of the attention has focused on the focal bone resorption in articular and periarticular bone associated with disorders such as rheumatoid arthritis (RA), the prototypical inflammatory joint disease. However, it is clear that many of the inflammatory rheumatic disorders have a marked effect on systemic bone remodeling and numerous studies have documented that osteoporosis and increased risk of fracture account for a substantial component of the morbidity associated with these conditions. In part, these adverse skeletal effects may be related to the therapies used to treat these diseases, as well as poor nutritional intake and other factors such as reduced physical activity that frequently occur in this population. This review will focus on the inflammatory rheumatologic disorders that target the articular and periarticular tissues. These entities include RA, juvenile idiopathic arthritis (JIA) (previously classified as juvenile rheumatoid arthritis), the seronegative spondyloarthropathies, and systemic lupus erythematosus (SLE). It is important to note, however, that many of the related immune-mediated rheumatic conditions such as systemic vasculitis may also be accompanied by adverse effects on skeletal remodeling and increased risk for osteoporosis, in part, related to the use of high-dose glucocorticoids and other therapies that adversely affect the skeleton.

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Repair of osteopenia in children with juvenile rheumatoid arthritis

J Pediatr

J Pediatr

J Pediatr

Lancet

Bone mineral content in normal U.S. whites

Quarterly changes in BMC at the radius and spine in young adults

Measurement of bone mineral content of the lumbar spine by dual energy x-ray absorptiometry in normal children: correlations with growth parameters

J Clin Endocrinol Metab

Critical years and stages of puberty for spinal and femoral bone mass accumulation during adolescence

J Clin Endocrinol Metab