May. 16, 2012

Predictors of Bone Density Changes in Children with Lupus

Predicting longitudinal trajectory of bone mineral density in paediatric systemic lupus erythematosus patients
Lim LS, Benseler SM, Tyrrell PN, Harvey E, Herbert D, Charron M, and Silverman ED. .Annals of the Rheumatic Diseases. 2012 Mar 22. doi: 10.1136/annrheumdis-2011-200805. [Epub ahead of print]

What is the topic?

People with lupus are at increased risk of osteoporosis, thinning or loss of bone tissue over time. This may result from disease mechanisms, steroid treatments, decreased physical activity, and/or vitamin D insufficiency (as a result of sun avoidance).

Childhood and adolescence are critical periods of bone growth, by the end of which over 90% of bone mass should have been accrued. Children with lupus are at increased risk of osteoporosis. However, it is unknown whether children with lupus may ever attain the peak level of genetically influenced bone mass if not reached by late adolescence.

What did the researchers hope to learn?

The researchers hoped to learn about the long-term outcomes of bone mass density (BMD) in children newly diagnosed with lupus.

Who was studied?

Sixty-eight children diagnosed with lupus at The Hospital for Sick Children in Toronto, Canada from June 2001 to June 2007 were included in the study.

How was the study conducted?

Inclusion criteria were as follows: a) age 5 years or older at lupus diagnosis; b) followed regularly at the SickKids Lupus Clinic in Toronto, Canada; c) initial bone scan (to determine BMD) study done within six months of lupus diagnosis; d) two follow-up bone scan studies approximately one year apart. Children with lupus were excluded from the study if they had a history of any bone diseases that may independently affect BMD or if they had received steroids before being seen at the SickKids Lupus Clinic in Toronto, Canada.

For each participant, the following demographic information was recorded at the time of lupus diagnosis: age, gender, ethnicity, family history of osteoporosis, pubertal status (defined as “pre-pubertal” or “pubertal”), height, and weight.

The following clinical information was recorded at the first and/or subsequent bone scan(s): evidence of neuropsychiatric or renal (kidney) disease, lupus disease activity (and its indicators in the blood), cumulative drug treatments (including cumulative dose of steroids taken prior to the first bone scan, as well as use of intravenous methylprednisone), permanent organ damage, and new major organ involvement between bone scans.

Each participant underwent three bone scans (separated approximately one year apart) on the lower portion of the backbone. Some participants having back pain or having BMD scores below a specific threshold underwent additional bone scans. At these times, information about blood indicators of lupus disease activity (blood count, erythrocyte sedimentation rate, complement proteins, and creatinine levels) and bone health (25-hydroxyvitamin D, intact parathyroid hormone, calcium, and phosphate) were collected. BMD measurements were classified as being either “low,” “low-normal,” or “abnormal” based on guidelines from the International Society of Clinical Densitometry.

A dietician assessed calcium and vitamin D intake for all participants at the start of steroid treatment. All participants received prednisone, as well as supplementation of vitamin D (at least 800 International Units per day) and calcium (about 1000 mg of elemental calcium per day).

What did the researchers find?

The participants were mostly Caucasian (although Asians and African-Americans were also included), pubertal girls who were an average age of 13 years old. About a third of the participants had major organ involvement upon entry to the study. During the three-year period over which the participants received three individual bone scans, the proportion of patients with new or active central nervous system involvement remained stable while, over the same time period, those with new or active kidney involvement decreased. Over the three-year period, participants were taking a variety of medications, including hydroxychloroquine, azathioprine, mycophenolate mofetil, cyclophosphamide, and methotrexate.

Over this three-year period, however, BMD decreased significantly. In addition, many participants in the “normal” or “low normal” group showed decreasing BMD into a lower category by the third bone scan. About 32% of the participants showed decreased BMD within six months of a lupus diagnosis. After three years of having lupus, 35% of participants deteriorated into a lower category of BMD while only 6% improved.

The trajectory (changes over time) of BMD in the children with lupus differed according to pubertal status, cumulative steroid doses, and weight. Children diagnosed with lupus while pubertal had lower BMD (and more BMD deterioration over time) than those diagnosed in pre-puberty. In addition, children with decreased weight or taking higher cumulative doses of steroids also showed a worse BMD trajectory over time. The effects of disease activity on BMD could not readily be determined from the current study.

The following were determined to not be major predictors of trajectory of BMD in children with lupus: ethnicity, major organ involvement at diagnosis, as well as blood levels of intact parathyroid hormone, 26-OHD (a storage form of vitamin D), and calcium.

What were the limitations of the study?

The study participants represent children with lupus who are relatively sicker than those seen in other care settings. Also, the bone scan methods used in this study have been criticized for being unable to provide information about characteristics of bone strength other than density. In addition, the BMD calculations used here correlate with height and, therefore, BMD may be underestimated here in shorter participants (although, calculations were made to attempt to correct this). Lastly, the researchers had no information about the physical activity exerted in the children with lupus, which may have impacted bone strength-related parameters.

What do the results mean for you?

In summary, BMD was decreased in pubertal (as compared to pre-pubertal) children, as well as in those with decreased weight or those taking higher cumulative doses of steroids. It is important to continue to encourage adequate calcium and vitamin D intake in all people with lupus, especially children, as well as to monitor long-term changes in BMD and blood indicators of bone health.

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