Q:

I am wondering if there are any recommendations for the management of osteopenia and low bone density in asthmatic children. Are there specific guidelines or established norms for BMD (bone mineral density) for comparison of dexa scan results & possible osteopenia in a 9 year old child? Are there any recommendations for asthma control in this population? Thank you

A:

 Thank you for your recent inquiry.

I am going to give you a partial answer, and then I will recruit a pediatric endocrinologist to help with the remainder of your question.

First of all, we will mention the treatment of asthma in a patient with osteopenia.

The treatment of asthma should not differ in patients who have osteopenia from the treatment in patients who do not. The same principles are employed. You should of course make a diligent effort to use as low a dose of inhaled corticosteroids as possible, and avoid systemic corticosteroids if possible. This would entail the standard principles of care as outlined in the EPR Guidelines. Of course, diligent efforts to minimize the use of corticosteroids both in systemic and inhaled forms should be made.As in all patients with asthma - the use of steroid-sparing drugs, adequate control of the allergic component if present, and assessing other factors that may worsen outcomes such as esophageal reflux, sinusitis, et cetera. These of course do not differ from the principles of therapy employed for patients who have asthma but no osteopenia.

Treatment of osteopenia in a child does bear some similarities to treatment in adults as well. We know that bisphosphonates are effective in children, and that two, alendronate and risedronate, have been approved for use in corticosteroid-induced osteoporosis. The three abstracts which are copied below substantiate the efficacy of this therapy.

However, beyond that, I believe that the help from a pediatric endocrinologist should be obtained. Therefore I have asked Dr. Jay Cohen, a pediatric endocrinologist, to help us respond to your inquiry with more detail in regards to the management of the osteopenia. I will forward Dr. Cohen's response to you as soon as we receive it.

Thank you again for your inquiry.

Abstract: Successful renal transplantation corrects many of the metabolic abnormalities associated with the development of renal osteodystrophy, but despite a well-functioning graft osteopenia, growth failure, spontaneous fractures, and avascular necrosis remain prevalent in adult and pediatric kidney recipients. A paucity of information exists regarding the effects of different therapies to prevent and treat bone loss in the renal transplant recipients. We constructed a design to study the effect of different modalities of treatment on bone mass in our renal transplant children. Among 93 patients who underwent renal transplantation at the age of 17 yr or less and were subjected to dual-energy X-ray absorptiometry (DEXA), we blindly randomized 60 patients who had osteopenia or osteoporosis (T-score = −1 by DEXA) in a prospective study. Their mean age at time of transplantation was 13.4 ± 4.3 yr. The mean duration after transplantation was 48 ± 34 months. The patients were classified randomly into four groups. Each group consisted of 15 patients: group 1 was the control group, group 2 received oral alfacalcidol 0.25 μg daily, group 3 received oral alendronate 5 mg daily, and group 4 received 200 IU/day nasal spray calcitonin. Parameters of bone turnover, calcium metabolism, and DEXA were measured before and after 12 months of treatment duration. The characteristics of all groups were comparable at the beginning of the study. At the lumber spine, bone mass density decreased from −2.4 to −2.8 in group 1, increased from −2.3 to −0.5 in group 2, from −2.3 to −1.9 in group 3, and from −2.3 to −1.0 in group 4. The four groups had similar patient profiles, serum creatinine, intact parathyroid hormone, osteocalcin, and deoxypyridinoline. This study confirmed the value of alfacalcidol and antiresorptive agents in the treatment of osteopenia and osteoporosis in young renal transplant recipients .These therapies were safe, tolerable, simple to administer and potentially applicable to other renal transplant patients. Pediatric Transplantation, Volume 8, Issue 4, pages 357–361, August 2004

Abstract
Objective
Osteopenia/osteoporosis is being increasingly reported as a complication of many chronic diseases, even in children. In this preliminary study, we evaluated the effect of an oral bisphosphonate (alendronate) on bone mass in children with diffuse connective tissue diseases.
Methods
Thirty-eight children with low bone mass were treated with alendronate for 1 year; 38 children who had the same primary disorders as the study patients but in a less severe form served as untreated control patients. We were also able to evaluate changes in bone mass (before and after alendronate) in 16 of the treated patients whose bone mineral density (BMD) had been routinely measured before the present study was initiated.
Results
BMD increased by a mean ± SD of 14.9 ± 9.8% (P < 0.002 versus baseline) in the treated patients (reaching the normal range in 13 patients), while the BMD was 2.6 ± 5% (not significant versus baseline) in the control group (15 had a decrease). Most interestingly, there was a large increase in BMD (15.3 ± 9.9%) after alendronate therapy in the 16 children who had their BMD followed up in the year before the study, during which time they had shown little increase in BMD (1.03 ± 6.3%), and often a decrease. Considering their condition, increases in the height of all patients was satisfactory. No new fractures were observed after alendronate therapy was initiated.
Conclusion
Bisphosphonates can be considered essential components of the treatment of secondary osteoporosis, not only in adults, but also in pediatric patients. Alendronate has a positive effect on secondary osteopenia/osteoporosis in children with connective tissue diseases
Arthritis & Rheumatism
Volume 43, Issue 9, pages 1960–1966, September 2000

Abstract
Objective: To evaluate in a double-blind, placebo-controlled clinical trial the safety and efficacy of intravenous pamidronate to treat osteopenia in nonambulatory children with cerebral palsy. Study design: Six pairs of subjects generally matched within each pair for age, sex, and race completed the protocol. One member of each pair randomly received plain saline placebo, the other pamidronate. Drug/placebo was administered intravenously daily for 3 consecutive days, and this 3-day dosing session was repeated at 3-month intervals for one year. Evaluations were continued for 6 months after the year of treatment. Bone mineral density (BMD) was measured in the distal femur, a site specifically developed for use in this contracted population, and the lumbar spine. Results: In the metaphyseal region of the distal femur, BMD increased 89% ± 21% (mean ± SEM) over the 18-month study period in the pamidronate group compared with 9% ± 6% in the control group. Age-normalized z scores increased from −4.0 ± 0.6 to −1.8 ± 1.0 in the pamidronate group and did not significantly change in the control group (−4.2 ± 0.3 to −4.0 ± 0.3). The first dosing with pamidronate caused a transient drop in serum calcium that was asymptomatic and not treated. No other potentially adverse effects were noted. Conclusions: In this small controlled clinical trial, pamidronate was found to be a safe and very effective agent to increase BMD in nonambulatory children with cerebral palsy. (J Pediatr 2002;141:644-51)

Sincerely,
Phil Lieberman, M.D.
 

We have received the response from Dr. Jay Cohen, which is copied below. Thank you again for your inquiry, and we hope this response is helpful to you.

Sincerely,
Phil Lieberman, M.D.

Response from Dr. Jay Cohen:
Thank you for your question.
There are no true guidelines for any treatment of osteopenia in children, but there are some guidelines existing for osteoporosis in children [see below]. Osteopenia in children is NOT a disease. It means the bone density (via DEXA or QCT scan) is lower than normal, but nor low enough to be considered osteoporosis and statistically may make up over 20% of the population. Therefore, we must be careful to not over treat this condition. Also, in children, adolescents and young adults it is important to use the Z-scores rather than T-scores because this describes the age matched controls; utilizing T-scores would cause falsely low bone mineral densities.

Guidelines for the prevention and treatment of adult glucocorticoid induced osteoporosis (GIO) have been produced by a number of countries over the past decade. These publications have mostly recognized the importance of primary prevention in high-risk individuals commencing glucocorticoid therapy, the place of bisphosphonates as a front-line therapeutic option, and the role of calcium and vitamin D supplementation. Most guidelines target adult individuals who take oral glucocorticoids continuously for 3-6 months in doses of 5-7.5 mg per day.

In adults, OP is commonly defined as a bone density of 2.5 standard deviations (SD) below the mean in dual emission x-ray absorptiometry (DXA). Osteopenia is defined as a bone density between 1.0 and 2.5 SD below the young adult mean. In the pediatric population, a somewhat different definition exists, requiring both a history of pathologic fractures and low bone mineral content or density. These criteria are fulfilled by the diagnosis of a single significant fracture in a long bone of the lower extremity, two fractures in the long bone of an upper extremity, or one vertebral compression fracture.

Bone density varies greatly with age. This is the reason the densitometry Z-score is used in the pediatric population and not the T-score usually used in adults. Z scores of -2 SD define OP.

The problem with pediatric DXA studies is the over-diagnosis of OP in children due to misinterpretation of data based on adult references. To help correct this misinterpretation, the Stanford reference graph was created based on an evaluation of 423 healthy children from various ethnicities. It is currently used for children by converting DXA data adjusted for age and sex.

Common laboratory tests for evaluation of OP include calcium, phosphate, bone alkaline phosphatase, vitamin D levels (most common vitamin D25), parathyroid hormone levels, and 24-hour urinary calcium and phosphate. More specific bone turnover markers include serum PINP (propeptide of type I procollagen) and carboxyterminal (PICP) propeptides of type I collagen as bone formation marker, and amino-terminal (NTX) and carboxyterminal (CTX) telopeptides of type I collagen as bone resorption markers.
 
While the guidelines for the treatment of OP in adults are widely accepted, the much less abundant data for children and adolescents with OP makes it harder to set clear guidelines for the pediatric population.
Daily oral intake of calcium is important for maintaining adequate homeostasis and facilitating bone remodeling and growth. The daily recommended intake (RDI) of calcium changes with age, from 500 mg at 1-3 years, to 800 mg for 4 to 8 year-olds, and 1300 mg for 9-18 years of age. Many children and adolescents do not ingest enough calcium to meet the RDI. Those at risk of OP should receive calcium supplements to insure adequate intake.

Likewise, vitamin D is crucial not only for bone health and maintaining serum calcium and phosphate levels, but may also be involved in promoting innate immunity. Vitamin D plasma levels in the general population have been decreasing in recent years in response to reduced sun exposure and outdoor activities, increased use of sunscreen and less exercise. The RDI for vitamin D was recently increased to 400 IU.

Bowden et al recently reported decreased levels of 25-hydroxyvitamin D levels among a large group of pediatric patients with OP and osteopenia. Although no direct connection with fracture risk was detected, they surmised that vitamin D supplementation in children with osteopenia and OP is advisable and may indeed reduce morbidity.

For primary prevention, use of bisphosphonates in children receiving corticosteroids for chronic disease is limited and currently is not recommended.

Bisphosphonate therapy over a long duration seem to be well-tolerated and safe according to two recent reviews that included a meta-analysis. Moreover, there seemed to be a consistent benefit in terms of increased BMD among the trials inspected.

In the past few years, there has been a move away from basing treatment decisions in adult patients with osteoporosis on T-scores alone towards the use of fracture probability estimates, which incorporate clinical risk factors with or without BMD measurement. With the availability of FRAX® in clinical practice and the inclusion of glucocorticoid therapy in the FRAX® algorithm for estimating fracture probability, newer guidelines for GIO have often become incorporated into more generic osteoporosis guidelines. This has NOT been transferred into the pediatric population yet. The impact of glucocorticoid therapy on fracture risk in FRAX® is based may underestimate fracture risk in current users. Also, the role of primary prevention in high-risk individuals may not be sufficiently emphasized because of the lack of specific guidelines for GIO.

Osteoporosis in children: pediatric and pediatric rheumatology perspective: a review Pediatric Rheumatology 2009, 7:16doi:10.1186/1546-0096-7-16 Gordon CM, Baim S, Bianchi ML, et al.: Special report on the 2007 Pediatric Position Development Conference of the International Society for Clinical Densitometry. South Med J 2008, 101:740-743.
 
http://www-stat-class.stanford.edu/pediatric-bones/ webcite.
Bishop N, Braillon P, Burnham J, et al.: Dual-energy X-ray aborptiometry assessment in children and adolescents with diseases that may affect the skeleton: the 2007 ISCD Pediatric Official Positions. J Clin Densitom 2008, 11:29-42.
 
Gafni RI, Baron J: Overdiagnosis of osteoporosis in children due to misinterpretation of dual-energy x-ray absorptiometry (DEXA). J Pediatr 2004, 144:253-257.
 
Greer FR, Krebs NF: Optimizing bone health and calcium intakes of infants, children, and adolescents.  Pediatrics 2006, 117:578-585.
 
Ward L, Tricco AC, Phuong P, et al.: Bisphosphonate therapy for children and adolescents with secondary osteoporosis. Cochrane Database Syst Rev 2007, (4):CD005324.
 
Bachrach LK, Ward LM: Clinical review 1: Bisphosphonate use in childhood osteoporosis.
J Clin Endocrinol Metab 2009, 94:400-409
 
Rudge S, Hailwood S, Horne A, et al.: Effects of once-weekly oral alendronate on bone in children on glucocorticoid treatment. Rheumatology (Oxford) 2005, 44:813-818.
Compston, J. E. Emerging consensus on prevention and treatment of glucocorticoid-induced osteoporosis. Curr. Rheumatol. Rep.9, 78-84 (2007).
1. University of Sheffield. FRAX®—
University of Sheffield. FRAX®—WHO Fracture Risk Assessment Tool [online] http:// www.shef.ac.uk/FRAX.
 
Regards to all,
Jay Cohen, MD, FACE, FAAP, CEC
Medical Director
The Endocrine Clinic, PC

AAAAI - American Academy of Allergy Asthma & Immunology