Disease/Disorder
Definition
Osteoporosis is a systemic, skeletal condition characterized by decreased bone mass, skeletal fragility, and deterioration of skeletal microarchitecture. Bone fragility is correlated with bone remodeling, quality, and turnover.1
In contrast to adults, osteoporosis in the pediatric population should not be made solely on densitometry. According to the International Society for Clinical Densitometry, pediatric osteoporosis is defined as the presence of one or more vertebral compression fractures not associated with either localized disease or significant (“high”) trauma or both a clinically significant fracture history and a bone mineral density (BMD) Z-score ≤ -2.0. A clinically significant fracture history includes
- Two or more long bone fractures by the age of 10 years
- Three or more long bone fractures by the age of 19 years.
Additionally, ISCD defined “low trauma” fractures as those occurring outside of motor vehicle accidents or falling from less than 10 feet. The same definition applied in the chronic illness setting, is conservatively adjusted to falling from a standing height or less, at no more than walking speed. The term osteopenia, used in adults to describe densitometry T scores of between -1 and -2.5, is not recommended in children and is instead replaced with “low bone mineral mass” or “low bone mineral density” in children with low Z-scores on densitometry without fracture history as above.2 These definitions and suggested criteria help prevent overdiagnosis and secondary unwarranted treatment.
Etiology
Primary osteoporosis in the pediatric population occurs due to an intrinsic skeletal defect of genetic or idiopathic origin. Osteogenesis Imperfecta (OI) is the most common condition, with an incidence of 1/15,000-20,000 births. Other causes include Idiopathic Juvenile Osteoporosis and Osteoporosis-pseudoglioma syndrome.3
Secondary osteoporosis in children is due to either the effects of a chronic disease process or the treatment, including immobility, on the skeleton. Specifically, there is a robust number and variety of childhood diseases treated by glucocorticoids (IBD, rheumatologic conditions, neuromuscular disease, and organ transplantation to name a few). Glucocorticoid exposure in childhood development may lead to impaired bone formation, accelerated bone resorption, increased 25 hydroxyvitamin D catabolism, decreased intestinal calcium absorption, and increased renal calcium excretion.4
Epidemiology including risk factors and primary prevention
In healthy children, 80% of fractures occur in the upper extremities. Risk factors for fractures include age, gender, previous fractures, genetic predisposition, poor nutrition, total body mass, vigorous physical activity and, equally, lack of physical activity.5
In non-ambulatory, disabled children, 70% of fractures are in the lower extremities, with over 50% occurring at the distal femur. Cerebral Palsy (CP) is the most common chronic pediatric disability associated with pediatric osteoporosis. The prevalence of osteoporosis in children with CP is up to 50%, and the annual fracture rate in patients with CP is approximately 5%, double that of a normal age-matched population.6
Main conditions associated with secondary osteoporosis include endocrine disorders (hypercortisolism, hyperthyroidism, hypogonadism; increased bone resorption), GI disorders (inflammatory bowel disease, malabsorption), cytokine-induced (leukemia, juvenile idiopathic arthritis, systemic lupus erythematosus), and immobility-induced (Duchenne Muscular Dystrophy, CP). Other commonly prescribed medications that may reduce BMD include anticonvulsants, chemotherapy, glucocorticoids.7
Patho-anatomy/physiology
Mechanical stress on bone is needed to stimulate osteoblasts to create bone as bones adjust their strength in proportion to the stress placed upon them. Peak childhood bone mass and quality dictates adult bone strength. Consequently, children with disabilities often have smaller, thinner bones with lower cortical mass due to reduced mechanical stress and weight bearing leading to increased fracture risk across the lifespan.8,9
Cytokine and growth factors produced by skeletal muscle and known as myokines are also involved in bone metabolism. Decreased activity, medications and procedures inhibiting muscle contraction may affect myokine secretion, potentiating the effects of impaired mobility on bone structure and strength.10
Sufficient levels of vitamin D and calcium are essential for bone strength and quality given mechanism of actions of modulation of calcium metabolism and reduction of PTH release, respectively. If deficient, this may lead to increased bone resorption.1 Children with disabilities are at increased risk for low calcium and vitamin D due to poor nutrition, oral motor feeding difficulties, gastrointestinal malabsorption, and limited sunlight exposure. Overall, the presence of malnutrition increases the likelihood of low BMD by nine-fold.11
Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)
Increased fracture risk has been associated with several factors:
- Prior fracture
- Increased body fat
- G-tube dependence
- Impaired cognition
- Decreased or no ambulation
- Minimal sun exposure
- Selected medication use
Without intervention, BMD continues to reduce, and the risk of osteoporosis increases over time.
Specific secondary or associated conditions and complications
Fractures can lead to several complications such as deformity in growing bones, contractures, pain, predisposition for pressure ulcers, respiratory and gastrointestinal difficulties, and secondary fractures. Femur fracture in a still ambulatory child with Duchenne Muscular Dystrophy may be the precipitating event resulting in premature loss of ambulation.
Essentials of Assessment
History
It is essential to evaluate for disorders of mineral metabolism and for undiagnosed acute or chronic systemic illnesses. This includes:
- Pertinent medical history
- Chronic medical disorders (e.g., CP, malabsorption syndromes, renal or liver disease)
- Endocrine disorders
- Pain in a limb or joint
- Previous fractures
- Nutrition history
- Significant weight gain or loss
- Typical daily food intake (Note that vegan and low/no milk diets are at higher risk of low calcium and vitamin D levels)
- Use of vitamins and supplements
- Medication use
- Steroids
- Anticonvulsants
- Proton pump inhibitors and H2 blockers
- Antidepressants (SSRIs and SNRIs)
- Chemotherapy
- Daily activity level
- Time per day spent weight bearing
- Daily sun exposure
- Time in a splint/cast
- Frequency of falls
- History of immobility
Physical examination
Weight, length, and skinfold thickness help estimate nutritional status. Postural and spinal exams may indicate vertebral involvement. Assessment of pubertal stage is valuable as children with delayed puberty may lack adequate sex steroids required for bone development. The presence of hip dysplasia, femoral anteversion, and contractures are important to note because they may affect imaging performed for BMD evaluation.
Functional assessment
The primary functional assessment tool is gait evaluation. Namely, in children with CP, the Gross Motor Functional Classification System (GMFCS) -Expanded and Revised is used to classify motor function ranging from community ambulators (I) to dependent, non-ambulators (V). Children with GMFCS levels of I-III demonstrate similar incidence for fractures as typically developing children. Those with GMFCS levels of IV-V were associated with an increased risk of fracture. Specifically, GMFCS levels of IV-V and concomitant AED therapy increased fracture risk two-fold.12
Laboratory studies
As indicated by history and exam (i.e., mineral disorders, inflammatory markers, bone marrow aspirate (in setting of childhood leukemia), endocrine hormone panel, celiac screen).13The National Osteoporosis Foundation uses the following criteria
- Vitamin D (25-hydroxyvitamin D) deficiency: < 30 ng/mL.
- Vitamin D insufficiency: 20-30 ng/mL.
- Preferred range for Vitamin D: 40 – 60 ng/mL. Calcium, phosphate, parathyroid hormone, and magnesium levels
- Alkaline phosphatase, osteocalcin, and N-telopeptide (markers of bone turnover)
- Urine calcium/creatinine level (to evaluate for hypercalciuria)
- When etiology is unclear, screening for malabsorption syndromes such as celiac disease or inflammatory bowel disease should be considered.
Imaging
Dual-energy x-ray absorptiometry (DXA) scan is the most commonly used and widely available technique to measure bone mass and density in children: it is highly reproducible, inexpensive, and confers low radiation exposure.12
It is important to note that an abnormal (low) bone mineral density (BMD) on DXA alone is not diagnostic for osteoporosis as BMD can be low in other settings, including, short stature, rickets, hypophosphatemia. Additionally, BMD may even be normal in fractures of both primary and secondary osteoporosis.13 The role of DXA is additional supporting data in comprehensive work up. Choice of skeletal site for DXA interpretation should be unique to patient characteristics. L1-L4 vertebrae and total body less head (TBLH) BMD are most widely used in children. However, in 2019, ISCD recommendations were updated to support DXA BMA evaluation at the distal forearm, proximal hip, and lateral distal femur in patients that require additional data or whole-body scans cannot be completed.13
Musculoskeletal quantitative computerized tomography (QCT), a volumetric measure of BMD of the hips or spine, is primarily a research technique used for BMD assessment and confers the highest radiation dose of any test of bone density. Clinically, QCT may be useful for measuring BMD of the spine of individuals with scoliosis, severe degenerative changes, vascular calcifications, disk space narrowing, compression fractures, or osteophytes, all of which can affect the accuracy of DXA results. According to the American College of Radiology, in these instances the following criteria are used in QCT trabecular spine BMD ranges:
- Osteoporosis: BMD < 80 mg/cm3
- Osteopenia: BMD 80-120 mg/cm3
- Normative: BMD >120 mg/cm3
Environmental
Fragility fractures for children with restricted mobility often occur during routine daily activities. Door thresholds, rug edges, and other obstacles can increase the risk for falls in ambulatory children. The presence of door jams, bed covers, and seat belt straps, which can catch the leg or arm of wheelchair users, may further increase the likelihood of falls and subsequent fracture.
Children with disabilities typically receive less sun exposure, which is the primary source of Vitamin D, than non-disabled children. The National Osteoporosis Foundation recommends 10 minutes of sun exposure to bare skin once or twice a day, depending on skin type, without sunscreen.14
Professional issues
Fragility fractures are most common in a physically vulnerable population. For non-verbal children presenting with fractures and no known traumatic event, the need for investigation of potential abuse may be warranted. Previous clinical assessment documenting fracture risk may help in the acute care assessment. It is also essential to fully address pain control needs for non-verbal children, assessing this through behavioral observations.
Rehabilitation Management and Treatments
Available or current treatment guidelines
Goals in management of pediatric osteoporosis and low bone mineral density are centered around early detection of vertebral fractures, optimizing peak bone mass, preventing pain, fractures and scoliosis, and improving function, and mobility.15
Bisphosphonates (BP) are a widely used medication for osteoporosis treatment with mechanism of inhibition of osteoclasts and inhibiting bone resorption. BP can be given orally or intravenously. Oral regimen is typically reserved for milder cases or in absence of vertebral fractures.15 2nd and 3rd generation BPs are most used in children. The optimal treatment duration has not been clearly defined; however, may consider discontinuation or progressive decrease of BP dosing for patients without a fracture during preceding year and have attained z-scores > -2.16 To date, BP therapy is used off label in pediatric age, but several studies have demonstrated safety and efficacy.15 In male, pediatric patients with DMD, administration of pamidronate or zoledronate resulted in resolution of decreased of back pain, stabilization of fractures, improvement of vertebral height, and partial prevention of new fractures.17 Another study demonstrated that glucocorticoid-treated children with underlying rheumatology conditions, inflammatory bowel disease, DMD achieved significant improvement in lumbar spine BMD z-score with IV zoledronate as compared to IV placebo.18 Optimal dosing, timing, and duration of BP in pediatric population remains largely undetermined due to lack of large-scale, randomized controlled trials and its off-label use.
Other pharmacological interventions, though less commonly used, may include denosumab and sclerostin inhibitors. Denosumab is a subcutaneous monoclonal antibody inhibitor which, similarly to BPs, inhibits bone resorption by inhibiting osteoclasts. It has only been used off-label in children with OI and currently does not represent a first line medication in children affected by osteoporosis but may be considered off-label in situations of renal failure or poor response to BPs if used with extreme precaution. Sclerostin inhibitors (such as Romosozumab, Setrusumab) are a novel class of monoclonal antibody inhibitors that through binding to sclerostin, have dual effect of inhibiting bone resorption and increase bone formation. There is no licensed indication for these medications currently in children, but both are undergoing further evaluation in trials for OI.15
At different disease stages
Conservative management for at-risk children includes improvement of nutrition (ensuring appropriate intake of vitamin D and calcium), encouraging physical activity (high impact if tolerable; consider physiotherapy to improve strength, balance, mobility), optimization of underlying conditions and osteotoxic medications, and reducing fall risk.15
Coordination of care
Treatment of osteoporosis in the pediatric population often involves a team-based approach. The team may include pediatric rehabilitation physicians, dieticians, endocrinologists, rheumatologists, and radiologists, who interpret the DXA scans; physical therapists and school personnel to ensure adequate weight-bearing activity and provide environmental guidelines for those at risk for fractures; and orthopedic surgeons to perform surgery to stabilize fragile or fractured bones and to correct bony deformities.
Patient & family education
Prevention remains the key component of osteoporosis treatment; therefore, early education of fracture risk factors and early initiation of weight-bearing activities and nutritional supplements are imperative. Safe transfers and safe means of mobility can be taught with the help of physical and occupational therapists. Children with disabilities are often handled by multiple family members, personal care workers, medical staff, and school personnel daily; thus, education of all caregivers about appropriate equipment use, transfer and positioning methods, and range of motion exercises is necessary. Safety support needs for ambulatory children may be high, and it may be challenging to balance the encouragement of weight bearing activity against the risk of injury from falls.
Emerging/unique interventions
The ultimate outcome measurement for treatment of osteoporosis is prevention and reduction of fractures and improving BMD. Pain relief, reduction of deformity, return to school, and participation in family activities are also measures of successful treatment outcomes.
Cutting Edge/Emerging and Unique Concepts and Practice
More frequent and higher-impact exercise through adapted physical education in school, community recreation, and mobility aids is encouraged for partially mobile children. Whole body vibration (WBV) continues to receive increased attention as treatment in pediatric patients to increase bone mass by increasing imposed muscular and mechanical forces. This occurs by low level mechanical stimulation to illicit strong anabolic response that ultimately may increase bone formation in trabecular bone. WBV could be considered additive or alternative to regular physical activity. A recent literature review demonstrated that WBV is a safe, non-pharmacological anabolic approach to increase bone mass in children/adolescents with low BMD and decreased activity levels in children with Down Syndrome, or severe motor disabilities, like CP. However, most of the prior studies analyzed for short durations (<6 months) and thus may not adequately reflect the bone modeling/remodeling cycle. In addition, further research is needed for treatment parameters (frequency, dosage, mechanism of vibration) and protocols.19
Gaps in the Evidence-Based Knowledge
Optimal timing and dosing of BP in the pediatric population is still undetermined. Bone mass accrual is fastest during puberty, which may be an optimal time to maximize pharmacologic intervention. There is no data to confirm whether individuals treated with BPs as children maintain bone density into adulthood or have decreased fracture rates over subsequent decades.15,16
Botulinum toxin, a frequently used management tool for abnormal muscle tone in children with cerebral palsy and other conditions, may affect BMD through decreased mechanic stress from muscles contraction and alterations in myokines. A 2019 animal study on rats to assess bone fragility and impact on osteocytes with muscle inactivity and immobilization from botulinum toxin injection in hindlimbs demonstrated reduced osteocyte lacunar density, decreased cortical thickness, and lower cancellous bone volume fraction in proximal tibial metaphysis.20 Further research is needed to better understand what effect botulinum toxin may have on bone health in pediatric patients as well as what factors may prevent deleterious changes such as injection dosage, toxin type and treatment interval.
Another treatment concept without clear recommendations at this time includes implementation of static, passive standing. A small, retrospective study of children with severe CP (GMFCS IV and V) was performed. The average standing time was 30 min/day (~210 min/week) and results demonstrated that all densitometries were improved (improved bone mineral content and bone mineral density in lumbar spine, total left hip, left femoral neck, TBLH). This study suggests that static, passive standing improves bone mineralization by limiting the bone resorption process.21 Further studies should be considered regarding a larger sample size, motor impairment specificity, and further analysis of treatment time range for the static standing protocol.
References
- Imamudeen N, Basheer A, Iqbal AM, Manjila N, Haroon NN, Manjila S. Management of Osteoporosis and Spinal Fractures: Contemporary Guidelines and Evolving Paradigms. Clin Med Res. 2022;20(2):95-106. doi:10.3121/cmr.2021.1612
- (2019). International Society for Clinical Densitometry. Pediatric position statement.
- Deguchi M, Tsuji S, Katsura D, Kasahara K, Kimura F, Murakami T. Current Overview of Osteogenesis Imperfecta. Medicina. 2021; 57(5):464. https://doi.org/10.3390/medicina57050464
- Ward LM. Glucocorticoid-Induced Osteoporosis: Why Kids Are Different. Front Endocrinol (Lausanne). 2020;11:576. Published 2020 Dec 16. doi:10.3389/fendo.2020.00576
- Saraff, V., & Hogler, W. (2015). Endocrinology and Adolescence: Osteoporosis in children: diagnosis and management. European Journal of Endocrinology, 185-197.
- Szalay, E. (2014). Bisphosphonate use in children with osteoporosis and other bone conditions. Journal of Pediatric Rehabilitation Medicine, 125-132.
- Ciancia S, van Rijn RR, Högler W, et al. Osteoporosis in children and adolescents: when to suspect and how to diagnose it. Eur J Pediatr. 2022;181(7):2549-2561. doi:10.1007/s00431-022-04455-2
- von Scheven, E., Corbin, K., Stefano, S., & Cimaz, R. (2014). Glucocorticoid-Associated Osteoporosis in Chronic Inflammatory Diseases: Epidemiology, Mechanisms, Diagnosis and Treatment. Pediatrics, 289-299.
- Sakka, S., & Cheung, M. (2020). Management of primary and secondary osteoporosis in children. Therapeutic Advances in Musculoskeletal Disease, 1-21.
- Kaji, H. (2016). Effects of myokines on bone. Bonekey Reports, 826.
- Alvarez, Z., & al, e. (2018). Bone mineral density and nutritional status in children with quadriplegic cerebral palsy. Archives of Osteoporosis, 17.
- Uddenfeldt Wort U, Nordmark E, Wagner P, Düppe H, Westbom L. Fractures in children with cerebral palsy: a total population study. Dev Med Child Neurol. 2013;55(9):821-826. doi:10.1111/dmcn.12178
- Ward LM, Weber DR, Munns CF, Högler W, Zemel BS. A Contemporary View of the Definition and Diagnosis of Osteoporosis in Children and Adolescents. J Clin Endocrinol Metab. 2020;105(5):e2088-e2097. doi:10.1210/clinem/dgz294
- (2021). National Osteoporosis Society.
- Ciancia S, Högler W, Sakkers RJB, et al. Osteoporosis in children and adolescents: how to treat and monitor?. Eur J Pediatr. 2023;182(2):501-511. doi:10.1007/s00431-022-04743-x
- Galindo-Zavala R, Bou-Torrent R, Magallares-López B, et al. Expert panel consensus recommendations for diagnosis and treatment of secondary osteoporosis in children. Pediatr Rheumatol Online J. 2020;18(1):20. Published 2020 Feb 24. doi:10.1186/s12969-020-0411-9
- Sbrocchi AM, Rauch F, Jacob P, et al. The use of intravenous bisphosphonate therapy to treat vertebral fractures due to osteoporosis among boys with Duchenne muscular dystrophy. Osteoporos Int. 2012;23(11):2703-2711. doi:10.1007/s00198-012-1911-3
- Ward LM, Choudhury A, Alos N, et al. Zoledronic Acid vs Placebo in Pediatric Glucocorticoid-induced Osteoporosis: A Randomized, Double-blind, Phase 3 Trial. J Clin Endocrinol Metab. 2021;106(12):e5222-e5235. doi:10.1210/clinem/dgab458
- Swolin-Eide D, Magnusson P. Does Whole-Body Vibration Treatment Make Children’s Bones Stronger?. Curr Osteoporos Rep. 2020;18(5):471-479. doi:10.1007/s11914-020-00608-0
- Gatti V, Ghobryal B, Gelbs MJ, et al. Botox-induced muscle paralysis alters intracortical porosity and osteocyte lacunar density in skeletally mature rats. J Orthop Res. 2019;37(5):1153-1163. doi:10.1002/jor.24276
- Barbier V, Goëb V, Klein C, et al. Effect of standing frames used in real life on bone remodeling in non-walking children with cerebral palsy. Osteoporos Int. 2022;33(9):2019-2025. doi:10.1007/s00198-022-06436-5
Original Version of the Topic
Jill R. Meilahn, DO, Deb McLeish, Michael Ward, MD, Elizabeth Moberg-Wolff. Osteoporosis/osteopenia in children. 9/20/2014.
Previous Revision(s) of the Topic
Christina Kokorelis, DO and Melissa Trovato, MD. Osteoporosis/osteopenia in children. 7/3/2018.
Melissa Trovato, MD, Anton Dietzen, MD. Osteoporosis/Low Bone Mineral Content in Children. 10/13/2021
Author Disclosure
Kristen Courtney, DO
Nothing to Disclose
Melissa Trovato, MD
Nothing to Disclose