# Osteoporosis in children and adolescents: when to suspect and how to diagnose it

**Authors:** Silvia Ciancia, Rick R. van Rijn, Wolfgang Högler, Natasha M. Appelman-Dijkstra, Annemieke M. Boot, Theo C. J. Sas, Judith S. Renes

PMC · DOI: 10.1007/s00431-022-04455-2 · European Journal of Pediatrics · 2022-04-06

## TL;DR

This paper reviews how to recognize and diagnose osteoporosis in children and adolescents, emphasizing the importance of early detection and treatment.

## Contribution

The paper provides a concise overview of risk factors and diagnostic approaches for pediatric osteoporosis, highlighting opportunities for pediatricians to improve bone health.

## Key findings

- Genetic and acquired disorders significantly impact bone health in children.
- Systematic approaches have been developed to diagnose and manage pediatric osteoporosis.
- Timely diagnosis and treatment can improve bone mass accrual in affected children.

## Abstract

Early recognition of osteoporosis in children and adolescents is important in order to establish an appropriate diagnosis of the underlying condition and to initiate treatment if necessary. In this review, we present the diagnostic work-up, and its pitfalls, of pediatric patients suspected of osteoporosis including a careful collection of the medical and personal history, a complete physical examination, biochemical data, molecular genetics, and imaging techniques. The most recent and relevant literature has been reviewed to offer a broad overview on the topic. Genetic and acquired pediatric bone disorders are relatively common and cause substantial morbidity. In recent years, there has been significant progress in the understanding of the genetic and molecular mechanistic basis of bone fragility and in the identification of acquired causes of osteoporosis in children. Specifically, drugs that can negatively impact bone health (e.g. steroids) and immobilization related to acute and chronic diseases (e.g. Duchenne muscular dystrophy) represent major risk factors for the development of secondary osteoporosis and therefore an indication to screen for bone mineral density and vertebral fractures. Long-term studies in children chronically treated with steroids have resulted in the development of systematic approaches to diagnose and manage pediatric osteoporosis.

Conclusions: Osteoporosis in children requires consultation with and/or referral to a pediatric bone specialist. This is particularly relevant since children possess the unique ability for spontaneous and medication-assisted recovery, including reshaping of vertebral fractures. As such, pediatricians have an opportunity to improve bone mass accrual and musculoskeletal health in osteoporotic children.
What is Known:• Both genetic and acquired pediatric disorders can compromise bone health and predispose to fractures early in life.• The identification of children at risk of osteoporosis is essential to make a timely diagnosis and start the treatment, if necessary.What is New:• Pediatricians have an opportunity to improve bone mass accrual and musculoskeletal health in osteoporotic children and children at risk of osteoporosis.• We offer an extensive but concise overview about the risk factors for osteoporosis and the diagnostic work-up (and its pitfalls) of pediatric patients suspected of osteoporosis.

What is Known:

• Both genetic and acquired pediatric disorders can compromise bone health and predispose to fractures early in life.

• The identification of children at risk of osteoporosis is essential to make a timely diagnosis and start the treatment, if necessary.

What is New:

• Pediatricians have an opportunity to improve bone mass accrual and musculoskeletal health in osteoporotic children and children at risk of osteoporosis.

• We offer an extensive but concise overview about the risk factors for osteoporosis and the diagnostic work-up (and its pitfalls) of pediatric patients suspected of osteoporosis.

## Linked entities

- **Diseases:** osteoporosis (MONDO:0005298), Duchenne muscular dystrophy (MONDO:0010679)

## Full-text entities

- **Genes:** ALPP (alkaline phosphatase, placental) [NCBI Gene 250] {aka ALP, PALP, PLAP, PLAP-1}, ASCC1 (activating signal cointegrator 1 complex subunit 1) [NCBI Gene 51008] {aka ASC1p50, CGI-18, SMABF2, p50}, SGMS2 (sphingomyelin synthase 2) [NCBI Gene 166929] {aka CDL, SMS2}, PTH (parathyroid hormone) [NCBI Gene 5741] {aka FIH1, PTH1}, NOTCH2 (notch receptor 2) [NCBI Gene 4853] {aka AGS2, HJCYS, hN2}, TMEM38B (transmembrane protein 38B) [NCBI Gene 55151] {aka C9orf87, D4Ertd89e, OI14, TRIC-B, TRICB, bA219P18.1}, CRTAP (cartilage associated protein) [NCBI Gene 10491] {aka CASP, LEPREL3, OI7, P3H5}, PLOD2 (procollagen-lysine,2-oxoglutarate 5-dioxygenase 2) [NCBI Gene 5352] {aka BRKS2, LH2, TLH}, TNFSF11 (TNF superfamily member 11) [NCBI Gene 8600] {aka CD254, ODF, OPGL, OPTB2, RANKL, TNLG6B}, SERPINF1 (serpin family F member 1) [NCBI Gene 5176] {aka EPC-1, OI12, OI6, PEDF, PIG35}, BMP1 (bone morphogenetic protein 1) [NCBI Gene 649] {aka OI13, PCOLC, PCP, TLD}, COL1A1 (collagen type I alpha 1 chain) [NCBI Gene 1277] {aka CAFYD, EDSARTH1, EDSC, OI1, OI2, OI3}, GGT1 (gamma-glutamyltransferase 1) [NCBI Gene 2678] {aka CD224, D22S672, D22S732, GGT, GGT 1, GGTD}, P3H1 (prolyl 3-hydroxylase 1) [NCBI Gene 64175] {aka GROS1, LEPRE1, OI8}, SOST (sclerostin) [NCBI Gene 50964] {aka CDD, DAND6, SOST1, VBCH}, CREB3L1 (cAMP responsive element binding protein 3 like 1) [NCBI Gene 90993] {aka C16DELp11.2, DEL16p11.2, OASIS, OI16}, SERPINH1 (serpin family H member 1) [NCBI Gene 871] {aka AsTP3, CBP1, CBP2, HSP47, OI10, PIG14}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, XYLT2 (xylosyltransferase 2) [NCBI Gene 64132] {aka PXYLT2, SOS, XT-II, XT2, xylT-II}, WNT3A (Wnt family member 3A) [NCBI Gene 89780], WNT1 (Wnt family member 1) [NCBI Gene 7471] {aka BMND16, INT1, OI15}, TRIP4 (thyroid hormone receptor interactor 4) [NCBI Gene 9325] {aka ASC-1, ASC1, HsT17391, MDCDC, SMABF1, ZC2HC5}, LRP1 (LDL receptor related protein 1) [NCBI Gene 4035] {aka A2MR, APOER, APR, CD91, DDH3, IGFBP-3R}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, SPARC (secreted protein acidic and cysteine rich) [NCBI Gene 6678] {aka BM-40, OI17, ON, ONT}, GORAB (golgin, RAB6 interacting) [NCBI Gene 92344] {aka GO, NTKLBP1, SCYL1BP1}, ANO5 (anoctamin 5) [NCBI Gene 203859] {aka GDD1, LGMD2L, LGMDR12, TMEM16E}, LRP6 (LDL receptor related protein 6) [NCBI Gene 4040] {aka ADCAD2, EVR8, OPTA4, STHAG7}, MMP2 (matrix metallopeptidase 2) [NCBI Gene 4313] {aka CLG4, CLG4A, MMP-2, MMP-II, MONA, TBE-1}, TNFRSF11A (TNF receptor superfamily member 11a) [NCBI Gene 8792] {aka CD265, FEO, LOH18CR1, ODFR, OFE, OPTB7}, PPIB (peptidylprolyl isomerase B) [NCBI Gene 5479] {aka CYP-S1, CYPB, HEL-S-39, OI9, SCYLP}, LRP5 (LDL receptor related protein 5) [NCBI Gene 4041] {aka BMND1, EVR1, EVR4, HBM, LR3, LRP-5}, IFIH1 (interferon induced with helicase C domain 1) [NCBI Gene 64135] {aka AGS7, Hlcd, IDDM19, IMD95, MDA-5, MDA5}, PYCR1 (pyrroline-5-carboxylate reductase 1) [NCBI Gene 5831] {aka ARCL2B, ARCL3B, P5C, P5CR, PIG45, PP222}, SP7 (Sp7 transcription factor) [NCBI Gene 121340] {aka OI11, OI12, OSX, osterix}, FKBP10 (FKBP prolyl isomerase 10) [NCBI Gene 60681] {aka BRKS, BRKS1, FKBP65, OI11, OI6, PPIASE}, MBTPS2 (membrane bound transcription factor peptidase, site 2) [NCBI Gene 51360] {aka BRESEK, IFAP, KFSD, KFSDX, OI19, OLMSX}, TNFRSF11B (TNF receptor superfamily member 11b) [NCBI Gene 4982] {aka OCIF, OPG, PDB5, TR1}, RIGI (RNA sensor RIG-I) [NCBI Gene 23586] {aka DDX58, RIG-I, RIG1, RLR-1, SGMRT2}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, COL1A2 (collagen type I alpha 2 chain) [NCBI Gene 1278] {aka EDSARTH2, EDSCV, OI4}, SEC24D (SEC24 homolog D, COPII component) [NCBI Gene 9871] {aka CLCRP2}, PDB5 [NCBI Gene 140777], MMP14 (matrix metallopeptidase 14) [NCBI Gene 4323] {aka MMP-14, MMP-X1, MT-MMP, MT-MMP 1, MT1-MMP, MT1MMP}, KDELR2 (KDEL endoplasmic reticulum protein retention receptor 2) [NCBI Gene 11014] {aka ELP-1, ERD2.2, OI21}, IFITM5 (interferon induced transmembrane protein 5) [NCBI Gene 387733] {aka BRIL, DSPA1, Hrmp1, OI5, fragilis4}
- **Diseases:** Short bowel syndrome (MESH:D012778), bone pain (MESH:D010146), Endocrine disorders (MESH:D004700), height loss (MESH:C000719188), spine tenderness (MESH:D063806), Turner syndrome (MESH:D014424), Duchenne Muscular Dystrophy (MESH:D020388), OI (MESH:D010013), cholestatic liver failure (MESH:D017093), bone resorption (MESH:D001862), skeletal defects (MESH:C567306), Leukemia (MESH:D007938), hearing loss (MESH:D034381), Juvenile Paget's Disease (MESH:C537701), Bruck Syndrome Type 2 (MESH:C537407), malnutrition (MESH:D044342), conditions (MESH:D020763), ligamentous laxity (MESH:C536012), inflammatory disorders (MESH:D007249), Gastro-intestinal disorders (MESH:D007410), disorders (MESH:D009358), TBLH (MESH:D006258), CDL (MESH:D003635), mass (MESH:C536030), Unknown (MESH:D009382), spondylometaphyseal dysplasia (MESH:C537501), osteoporotic (MESH:D058866), bone formation (MESH:D058426), hematological and oncological disorders (MESH:D006402), VFs (MESH:C535781), Malabsorption syndromes (MESH:D008286), SMABF2 (OMIM:616867), OI 1,2,3,4 (MESH:C536044), Cushing's disease (MESH:D047748), celiac (MESH:D002446), BMD (MESH:D001851), Unclear Cutis laxa (MESH:D003483), SMABF1 (OMIM:616866), genetic defect (MESH:D030342), metabolic disorders (MESH:D008659), asthma (MESH:D001249), Inflammatory bowel disease (MESH:D015212), idiopathic arthritis (MESH:D001168), rickets (MESH:D012279), Multicentric osteolysis, nodulosis, and arthropathy (MESH:C536051), Geroderma osteodysplasticum (MESH:C537799), bone fractures (MESH:D050723), Osteoporosis (MESH:D010024), muscle impairment (MESH:D009135), AR (MESH:D013734), growth delay (MESH:D006130), Klinefelter syndrome (MESH:D007713), dentinogenesis imperfecta (MESH:D003811), FEO (MESH:C536335), joint laxity (MESH:D007593), Gnathodiaphyseal dysplasia (MESH:C536039), osteomalacia (MESH:D010018), IJO (MESH:C537700), Back pain (MESH:D001416), muscle tension (MESH:D018781)
- **Chemicals:** creatinine (MESH:D003404), bisphosphonate (MESH:D004164), 25-hydroxy vitamin D (MESH:C104450), phosphate (MESH:D010710), magnesium (MESH:D008274), steroid (MESH:D013256), hydroxyapatite (MESH:D017886), calcium (MESH:D002118), lipids (MESH:D008055), vitamin D (MESH:D014807), tetracycline (MESH:D013752), cortisol (MESH:D006854), estradiol (MESH:D004958), water (MESH:D014867), growth hormone (MESH:D013006), GCs (-), testosterone (MESH:D013739),  (MESH:D050071)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## References

111 references — full list in the complete paper: https://tomesphere.com/paper/PMC9192469/full.md

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Source: https://tomesphere.com/paper/PMC9192469