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State-of-the-Art Pediatrics

May 2022

The Child With Multiple Fractures – When to Suspect Something More Than an Accident-Prone Child?


Co-author: Darcy Weidemann, MD, MHS | Pediatric Nephrology | Associate Professor of Pediatrics, UMKC School of Medicine

Co-author: Uri Alon, MD | Director of Bone and Mineral Disorders Clinic | Professor of Pediatrics, UMKC School of Medicine

Column Editor: Amita Amonker, MD, FAAP | Pediatric Hospitalist | Assistant Professor of Pediatrics, UMKC School of Medicine 


Fractures are commonly encountered in general pediatric practice. Up to 40%-50% of the population experiences at least one fracture by adulthood, and up to one-quarter of children may experience more than one fracture. However, recurrent fractures may also be a sign of a primary or secondary bone fragility disorder. Therefore, general pediatricians may frequently encounter the dilemma of how to distinguish between a healthy child with normal bone health versus a child with underlying medical conditions who may warrant further workup.

The term osteoporosis refers literally to “porous bone.” The condition is characterized by too little bone formation, excessive bone loss or a combination of both. Osteoporotic bone is at high risk for fractures even after a minor trauma. Rare in children and adolescents, osteoporosis is often secondary to an underlying genetic disorder or medical condition, and can be an adverse effect of certain medications. Primary bone diseases such as osteogenesis imperfecta (OI), hypophosphatasia or collagen vascular diseases are rarer but tend to present with severe disease. The table below highlights important primary and secondary causes of increased bone fragility in childhood. Impaired bone health in children as a complication of many chronic conditions has become increasingly recognized. Medical advancements in the treatment of many chronic pediatric conditions such as cystic fibrosis, inflammatory bowel disease, pediatric cancer and neurological disorders such as static encephalopathies have led to a dramatically improved life expectancy. However, the nature of these diseases, at times combined with their long-term treatment, can result in detrimental effects on bone health, leading to osteoporosis, fractures and poor quality of life.

Overall bone health should be assessed in all children with clinically significant new fractures caused by low- or moderate-energy trauma; involving vertebrae or long bones of the extremities; and not including fractures of the nose, skull, fingers or toes.1 In children, non-accidental trauma should be excluded. Bone health should be formally assessed in the case of one or more vertebral fracture, two or more clinically significant fractures before the age of 10 years, or three or more clinically significant fractures before age 16 years.2

The first-line evaluation is to identify risk factors for bone fragility, establish baseline imaging studies and initiate appropriate supportive treatment to reduce the risk for future fragility factors. A detailed history and physical examination are mandatory. Family history of multiple fractures may suggest a primary hereditary bone disorder. A detailed nutritional assessment of calcium, vitamin D and other macronutrients may identify vitamin and nutritional deficiencies. A physical examination should evaluate for potential features of underlying collagen or connective tissue disorder, and also examine for spinal tenderness or deformity. At a minimum, a biochemical assessment should include: serum calcium, phosphate, creatinine, parathyroid hormone, 25-hydroxy vitamin D (25-OH-D), alkaline phosphatase and urinary calcium-to-creatinine ratio. Baseline dual-energy X-ray absorptiometry (DXA) study is key to an initial radiological examination. The study should be conducted in a facility where pediatric-specific software is available to establish appropriate Z scores.

An important initial treatment strategy for osteoporosis is supplementation with minerals such as calcium and vitamin D, which may begin in the primary care office and with the assistance of a nutritionist. Referral to a specialist in bone and mineral disorders is warranted in children with features that suggest a primary bone disorder or have a BMD Z score less than -2. The most frequently used pharmacological intervention for osteoporosis in children is bisphosphonate therapy. It decreases osteoclast function and inhibits bone resorption, allowing osteoblasts to improve mineralization and leading to higher cortical bone thickness and BMD. Due to the risk for flu-like symptoms and potential for transient hypocalcemia, bisphosphonate therapy should be restricted to centers with appropriate experience in using it.3 Collaboration with physical therapy to establish a weight-bearing physical activity program is an important component of multidisciplinary treatment. No consensus exists about when to refer for genetic analysis, although we recommend genetic analysis of children with fractures and osteoporosis when secondary causes have been excluded.

Regardless of the cause, identifying children at high risk for fractures is especially important because this condition occurs during the child’s peak bone-building years. Children accumulate bone mass from birth through young adulthood. Adolescence and early adulthood are critical time periods for establishing bone mass for a lifetime. Therefore, timely diagnosis and treatment of osteoporosis can significantly impact long-term outcomes and health-related quality of life.

At Children’s Mercy Kansas City, a bone and mineral specialty clinic exists to serve patients with a variety of bone and mineral disorders. A multidisciplinary team is engaged to determine timely diagnosis and appropriate management of children with bone fragility disorders. We have led pioneering efforts demonstrating the safety and efficacy of bisphosphonates in children.3 Appointments can be scheduled by calling (816) 234-3030.


Table 1. Conditions Associated With Increased Bone Fragility and Risk for Fractures

Primary Conditions Secondary Conditions

Connective Tissue Disorders

  • Ehlers-Danlos syndrome
  • Homocystinuria
  • Marfan syndrome


  • Growth hormone deficiency
  • Hypercortisolism
  • Hyperparathyroidism
  • Hypogonadism

Defective bone mineralization

  • Hypophosphatasia

Infiltrative Conditions

  • Leukemia/lymphoma
  • Thalassemia

Impaired collagen gene expression

  • Osteogenesis imperfecta
  • (COL1A1, COL1A2 mutations)

Muscular Disorders

  • Immobility
  • Duchenne muscular dystrophy

Impaired collagen cross-link formation

  • Bruck syndrome

Rheumatological Disorders

  • Inflammatory bowel disease
  • Juvenile idiopathic arthritis

Impaired cell signaling and osteoblasts

  • Osteoporosis pseudoglioma syndrome

Renal Disorders

  • Chronic kidney disease
  • Idiopathic hypercalciuria

Idiopathic juvenile osteoporosis

  • Cause unknown


  • Glucocorticoids
  • Antiepileptic medications
  • Anticoagulants
  • Loop diuretics

Nutritional Deficiencies

  • Anorexia nervosa
  • Celiac disease
  • Cystic fibrosis
  • Vitamin D deficiency rickets



  1. Bishop N, Arundel P, Clark E, et al; International Society of Clinical Densitometry. Fracture prediction and the definition of osteoporosis in children and adolescents: the ISCD 2013 Pediatric Official Positions. J Clin Densitom. 2014;17(2):275-280. PMID: 24631254. doi:10.1016/j.jocd.2014.01.004
  2. Mäyränpää MK, Viljakainen HT, Toiviainen-Salo S, Kallio PE, Mäkitie O. Impaired bone health and asymptomatic vertebral compressions in fracture-prone children: a case-control study. J Bone Miner Res. 2012;27(6):1413-1424. PMID: 22367922. doi:10.1002/jbmr.1579
  3. Sebestyen JF, Srivastava T, Alon US. Bisphosphonates use in children. Clin Pediatr (Phila). 2012;51(11):1011-1024. PMID: 22935217. doi:10.1177/0009922812452118