How is juvenile osteoporosis diagnosed?

Diagnosis of juvenile osteoporosis is often not made until the child has a broken bone. In
addition to a complete medical history and physical examination, diagnostic procedures for
juvenile osteoporosis may include:

 Family medical history

 Skeletal X-rays. A diagnostic test that uses invisible electromagnetic energy beams to
produce images of internal tissues, bones, and organs onto film.
 Bone density test. A diagnostic procedure to determine bone mineral content and
skeletal changes, such as bone loss. Unfortunately, there haven't been enough tests
done on children to determine what is normal.
 Blood tests. Tests to measure serum calcium and potassium levels

Diagnostic methods

Diagnosis is based on clinical presentation, skeletal X-rays and bone density tests (dual-
energy X-ray absorptiometry, dual photon absorptiometry and quantitative computed
tomography).

the diagnosis of osteoporosis in children can be made in the presence of

i) a combination of size-corrected low bone mineral density (BMD) of more than two S.D.
below the mean and a significant history of low trauma fractures, arbitrarily defined as the
presence of either two or more long bone fractures by the age of 10 years or three or more
long bone fractures at any age, up to the age of 19 years
Kombinasi kepadatan mineral tulang rendah yang dikoreksi (BMD) lebih dari
dua S.D. Di bawah rata-rata dan riwayat patah tulang trauma yang
signifikan, yang secara sewenang-wenang didefinisikan sebagai adanya dua
atau lebih patah tulang panjang pada usia 10 tahun atau tiga atau lebih
patah tulang panjang pada usia berapapun, sampai usia 19 tahun
or
ii) or one or more vertebral fractures (VFs) in the absence of high energy trauma or local
disease, independent of BMD
Atau satu atau lebih fraktur vertebra (VFs) tanpa adanya trauma energi
tinggi atau penyakit lokal, terlepas dari BMD

diagnostic tools: Every child referred for bone assessment deserves a routine measurement of
bone metabolism including serum alkaline phosphatase, calcium, phosphate, vitamin D and
urinary bone mineral excretion, as a minimum, in addition to a detailed history of growth and
nutrition. Measurement of bone turnover markers is reserved for specific cases and research.
Here, we describe the specific tools that are useful in the diagnosis of osteoporosis.
Setiap anak yang dirujuk untuk penilaian tulang layak mendapat pengukuran
rutin metabolisme tulang termasuk serum alkaline phosphatase, kalsium,
fosfat, vitamin D dan ekskresi mineral tulang kencing, minimal, selain
riwayat pertumbuhan dan gizi yang terperinci. Pengukuran penanda perputaran
tulang dicadangkan untuk kasus dan penelitian spesifik. Di sini, kami
menggambarkan alat spesifik yang berguna dalam diagnosis osteoporosis.
Assessment of bone mass and structure (penilaian massa dan struktur tulang)
Dual energy X-ray absorptiometry (DXA) remains the technique of choice to measure bone
mass as it is highly reproducible, commonly available and relatively inexpensive and has low
radiation exposure. Lumbar spine (LS) and total body less head are the preferred sites for
measuring bone mineral content in grams or areal BMD (in grams/cm2) in children (10).
BMD values for children are expressed as age- and sex-specific S.D. scores (Z-scores), but
they also depend on body size, ethnicity, pubertal staging and skeletal maturity. As a result of
DXA’s twodimensional measurement, BMD can be grossly underestimated in children with
short stature. (11, 12) Hence, in children with short stature, BMD requires adjustment for
height or bone volume such as bone mineral apparent density (BMAD, in g/cm3) to avoid
gross overestimation of osteoporosis (13). BMAD is the most accurate method to predict VFs
(14). Despite its pitfalls, DXA is recommended as a monitoring tool in children with chronic
disease, who are at a risk of developing osteoporosis and those who are already on treatment
to guide future management (15). An alternate technique used in children with spinal
deformity or contractures is the lateral femur DXA scan (16)
Dual energy X-ray absorptiometry (DXA) tetap menjadi teknik pilihan untuk
mengukur massa tulang karena sangat dapat direproduksi, biasanya tersedia
dan relatif murah dan memiliki paparan radiasi rendah. Lumbar spine (LS)
dan total body less head adalah situs pilihan untuk mengukur kandungan
mineral tulang dalam gram atau areal BMD (dalam gram / cm2) pada anak-anak
(10). Nilai BMD untuk anak-anak dinyatakan sebagai S.D. usia dan jenis
kelamin. Skor (skor Z), tapi juga bergantung pada ukuran tubuh, etnisitas,
stadium pubertas dan kematangan kerangka. Sebagai hasil pengukuran
twodimensional DXA, BMD bisa sangat diremehkan pada anak-anak dengan
perawakan pendek. (11, 12) Oleh karena itu, pada anak-anak dengan perawakan
pendek, BMD memerlukan penyesuaian untuk tinggi atau volume tulang seperti
kerapatan mineral tulang (BMAD, g / cm3) untuk menghindari perkiraan
berlebihan osteoporosis (13). BMAD adalah metode yang paling akurat untuk
memprediksi VFs (14). Meskipun ada perangkap, DXA direkomendasikan sebagai
alat pemantauan pada anak-anak dengan penyakit kronis, yang berisiko
terkena osteoporosis dan mereka yang sudah menjalani perawatan untuk
memandu manajemen masa depan (15). Teknik alternatif yang digunakan pada
anak-anak dengan deformitas atau kontraksi spinal adalah pemindaian DXA
lateral femur.
A large cross-sectional study demonstrated an association of increased fracture risk (6–15%)
with every one S.D. reduction in distal femur BMD (17). VFs in children can present with
backache but are often asymptomatic. They are a significant cause of morbidity and an
indicator of future incident VFs in children (18, 19) and adults (20). Children also have the
unique ability of bone reshaping due to their growth potential. Given their importance in the
diagnosis of osteoporosis, and that they can be asymptomatic and go undetected, assessment
of vertebral morphometry is essential. The lateral spine X-ray currently is the most
commonly used imaging technique to evaluate VFs in children but radiation exposure is high.
Sebuah penelitian cross-sectional besar menunjukkan adanya hubungan antara
risiko patah tulang (6-15%) dengan setiap orang S.D. Penurunan BMD distal
femur (17). VF pada anak-anak dapat hadir dengan sakit punggung tapi sering
tanpa gejala. Mereka adalah penyebab morbiditas yang signifikan dan
merupakan indikator kejadian VF di masa depan pada anak-anak (18, 19) dan
orang dewasa (20). Anak-anak juga memiliki kemampuan unik pembentukan
tulang karena potensi pertumbuhannya. Mengingat pentingnya diagnosis
osteoporosis, dan asimtomatik dan tidak terdeteksi, penilaian morfometri
vertebik sangat penting. Sinar X tulang belakang lateral saat ini adalah
teknik pencitraan yang paling umum digunakan untuk mengevaluasi VF pada
anak-anak namun paparan radiasi tinggi.
The Genant semiquantitative method is a technique used to grade VF in adults (21), with
good reproducibility in children (22). The newest generation of DXA scanners allows VF
assessment (VFA) to be performed on lateral scanning. Although radiation doses vary with
different scan modes in comparison to spine X-rays (23). VFA only uses a fraction (w1%) of
radiation exposure and compares with the daily dose of natural background radiation (24).
Although VFA may not have the spatial resolution of lateral spine X-rays and paediatric VFA
on older Hologic models was not satisfactory (25), the image quality on the new Lunar iDXA
scanner appears promising (Fig. 1).
Metode semiquantitative Genant adalah teknik yang digunakan untuk menilai
VF pada orang dewasa (21), dengan reproduktifitas yang baik pada anak-anak
(22). Generasi terbaru dari pemindai DXA memungkinkan penilaian VF (VFA)
dilakukan pada pemindaian lateral. Meskipun dosis radiasi berbeda dengan
mode pemindaian berbeda jika dibandingkan dengan sinar-X tulang belakang
(23). VFA hanya menggunakan pecahan (w1%) paparan radiasi dan
membandingkannya dengan dosis harian radiasi latar alami (24).
Meskipun VFA mungkin tidak memiliki resolusi spasial sinar X lateral dan
VFA pediatrik pada model Hologia yang lebih tua tidak memuaskan (25),
kualitas gambar pada pemindai iDXA Lunar baru tampak menjanjikan.

Validation studies for VF detection in children using this technique are underway.
Quantitative computed tomography (QCT) and peripheral QCT (pQCT) have the advantage
of measuring cortical geometry and volumetric densities of both trabecular and cortical bone,
thus providing information not attainable through DXA. Using pQCT in children with
cerebral palsy demonstrated smaller and thinner bones rather than lower cortical BMD (26).
pQCT also identified that cortical thickness, and not density, is the main bone variable
affected by growth hormone deficiency and treatment (27). Reproducibility and positioning
remain a problem with pQCT. It is specifically useful for children with spinal deformities,
contractures or metallic implants, whereas DXA imaging can prove challenging in these
children. The newest technique is high-resolution pQCT, which has the spatial resolution to
measure trabecular geometry and microarchitectural changes resulting from treatment.
However, it is expensive, limited to imaging extremities and currently mainly used for
research purposes (28).
Studi validasi untuk deteksi VF pada anak-anak dengan menggunakan teknik
ini sedang berlangsung. Kuantitatif computed tomography (QCT) dan QCT
perifer (pQCT) memiliki keuntungan untuk mengukur geometri kortikal dan
kepadatan volumetrik tulang trabekuler dan kortikal, sehingga memberikan
informasi yang tidak dapat dicapai melalui DXA. Menggunakan pQCT pada anak-
anak dengan cerebral palsy menunjukkan tulang yang lebih kecil dan lebih
tipis daripada BMD kortikal yang lebih rendah (26). PQCT juga
mengidentifikasi bahwa ketebalan korteks, dan bukan kepadatan, adalah
variabel tulang utama yang dipengaruhi oleh defisiensi hormon pertumbuhan
dan pengobatan (27). Reprodusibilitas dan posisi tetap menjadi masalah
dengan pQCT. Hal ini secara khusus berguna untuk anak-anak dengan kelainan
bentuk tulang belakang, kontraktur atau implan logam, sedangkan pencitraan
DXA dapat membuktikan tantangan pada anak-anak ini. Teknik terbaru adalah
resolusi tinggi pQCT, yang memiliki resolusi spasial untuk mengukur
geometri trabekuler dan perubahan mikroarsitektur akibat perlakuan. Namun,
harganya mahal, terbatas pada ekstremitas pencitraan dan saat ini terutama
digunakan untuk tujuan penelitian

Another method used to measure peripheral bone geometry and density is digital X-ray
radiogrammetry, which estimates BMD by hand radiographs in children. However, this
technique, as well as quantitative ultrasound and magnetic resonance imaging, are less
commonly used in clinical practice since validation studies establishing their association with
VF or non-VF are missing. Trans-iliac bone biopsy with tetracycline labeling provides the
ultimate, invasive diagnostic information on bone material properties, bone formation and
resorption activities as well as histomorphometry. Biopsies are useful in establishing the
diagnosis and defining bone tissue characteristics and metabolic activity in some cases such
as Idiopathic juvenile osteoporosis (IJO). However, it is used infrequently as a
treatmentmonitoring tool in children since it requires general anaesthesia, and response to
therapy, in most cases, can be adequately assessed using imaging or fracture history. As such,
biopsies are limited to highly specialized centres and research.
Metode lain yang digunakan untuk mengukur geometri dan kepadatan tulang
perifer adalah radiogramogram sinar-X digital, yang memperkirakan BMD
dengan radiografi tangan pada anak-anak. Namun, teknik ini, serta
ultrasound kuantitatif dan pencitraan resonansi magnetik, kurang umum
digunakan dalam praktik klinis sejak studi validasi yang menetapkan
hubungan mereka dengan VF atau non-VF hilang. Biopsi tulang trans-iliaka
dengan pelabelan tetrasiklin memberikan informasi diagnostik invasif dan
utama pada sifat-sifat tulang, pembentukan tulang dan aktivitas resorpsi
serta histomorfometri. Biopsi berguna dalam menegakkan diagnosis dan
menentukan karakteristik jaringan tulang dan aktivitas metabolik pada
beberapa kasus seperti osteoporosis remaja Idiopatik (IJO). Namun, jarang
digunakan sebagai alat pengaktifan perawatan pada anak-anak karena
memerlukan anestesi umum, dan respons terhadap terapi, pada kebanyakan
kasus, dapat dinilai secara memadai dengan menggunakan riwayat pencitraan
atau rekahan. Dengan demikian, biopsi terbatas pada pusat dan penelitian
yang sangat khusus.

Mobility, muscle and functional tests

Increasing emphasis is being placed on improving functional outcomes, muscle strength and
mobility in children with osteoporosis. There are various functional tests used, for example
the 6-min walk test (32), Bruininks Oseretsky Test of Motor Proficiency (33), gross-motor
function measure (34), Childhood Health Assessment Questionnaire score (35) and the
widely used faces pain scale (36). Specific muscle force and power tests include the chair-rise
test, mechanography (legs) (37, 38) and grip force testing by dynamometry (39), among
others. Since these tests measure different functional variables, selection depends on disease-
specific or case-specific deficits and protocols need to be established.
Penekanan yang meningkat sedang dilakukan pada peningkatan hasil
fungsional, kekuatan otot dan mobilitas pada anak-anak dengan osteoporosis.
Ada berbagai tes fungsional yang digunakan, misalnya uji coba 6 menit (32),
Uji Oeketsky Uji Daya Bermotor Motor (33), ukuran fungsi motorik kasar
(34), skor Kuesioner Penilaian Kesehatan Anak (35) dan yang digunakan
secara luas Menghadapi skala nyeri (36). Uji kekuatan dan kekuatan khusus
meliputi uji kenaikan kursi, mekanika (kaki) (37, 38) dan pengujian
kekuatan pegangan dengan dinamika (39), antara lain. Karena tes ini
mengukur variabel fungsional yang berbeda, seleksi tergantung pada defisit
spesifik penyakit dan spesifik kasus dan protokol perlu ditetapkan.

Diagnosis
The World Health Organization defined a normal bone mineral density for adults as being
between zero and + 1 standard deviation (SD) in relation to average values observed in
healthy young adults (t-score). For children these values must be adjusted for age and sex
(zscore). Osteopenia is defined as being when bone mineral density is between -1 and -2.5
SD and osteoporosis as when it is below -2.5 SD.4 Golding et al.9 demonstrated that a
reduction of one SD in total body bone density doubles the risk of fractures in girls.
Indications that bone mineral density (BMD) should be investigated are: estrogen deficiency,
hypogonadism, a suspicion of osteopenia due to x-ray findings, primary asymptomatic
hyperparathyroidism, chronic diseases and therapy with corticosteroids.
Organisasi Kesehatan Dunia mendefinisikan kepadatan mineral tulang normal
untuk orang dewasa sebagai antara nol dan + 1 standar deviasi (SD) dalam
kaitannya dengan nilai rata-rata yang diamati pada orang dewasa muda yang
sehat (t-score). Bagi anak-anak nilai ini harus disesuaikan dengan usia dan
jenis kelamin (zscore). Osteopenia didefinisikan sebagai kepadatan mineral
tulang antara -1 dan -2,5 SD dan osteoporosis seperti pada saat di bawah -
2,5 SD.4 Golding dkk.9 menunjukkan bahwa pengurangan satu SD pada kepadatan
tulang tubuh total melipatgandakan risiko Patah tulang pada anak perempuan
Indikasi bahwa kepadatan mineral tulang (BMD) harus diselidiki adalah:
defisiensi estrogen, hipogonadisme, kecurigaan osteopenia karena temuan
sinar-x, hiperparatiroidisme asimtomatik asimtomatik, penyakit kronis dan
terapi dengan kortikosteroid.

Imaging methods
The method employed for measuring bone mineral density (BMD) in children is dual energy
X-ray absorption (DEXA). Dual energy X-Ray absorption measures BMD both in the axial
and the appendicular skeleton and is therefore capable of evaluating both trabecular and
cortical bone. The DEXA method is considered the method of choice for measuring bone
mass because it is fast, precise and causes low levels of radiation exposure. Bone
densitometry detects bone mass losses of less than 5%, while the x-ray system detects losses
of 30 to 50%. The interpretation of DEXA in children is a challenge because of the changes
in bone size and geometry that occur during their growth and development. Correct
interpretation of the data must take into account skeletal maturity, pubertal development,
ethnic origins, weight and height of the patient. Bone mass is recorded in terms of bone
mineral content (BMC, in grams) and bone mineral density (BMD, in g/cm2), and both can
be influenced by the size of the bones. Although BMD is adjusted to the bone area scanned,
this does not correct differences in bone thickness. Thus, the true density is overestimated in
large bones and underestimated in small ones. In order to avoid this problem a number of
different mathematical models have been developed to estimate the volume of bone (g/cm3).
In order to correct the bone mineral content of the whole body for bone size, Molgaard et al.
have suggested taking the height and bone are of the individual into account. Despite the lack
of consensus on the best method for adjusting for bone size, skeletal age and pubertal
development should be considered when interpreting pediatric densitometric studies. Other
methods used to measure BMD include quantitative computerized tomography (QCT) and
quantitative ultrasound (QUS). Quantitative computerized tomography measures volumetric
BMD, but the patient is subjected to a high dose of radiation, which can be minimized by
using peripheral quantitative computerized tomography (pCTQ). Quantitative ultrasound is
often used to assess the BMD of calcaneus and phalanges. It is an easily performed
examination, of low cost and does not involve radiation. During childhood, however, the
bone macrostructure of the areas being evaluated is constantly changing, which compromises
the sensitivity of this examination.
Metode yang digunakan untuk mengukur kepadatan mineral tulang (BMD) pada
anak-anak adalah penyerapan sinar-X energi ganda (DEXA). Dual-energi X-Ray
penyerapan pengukuran BMD baik dalam aksial dan kerangka appendicular dan
karena itu mampu mengevaluasi kedua trabecular dan
Tulang kortikal Metode DEXA dianggap sebagai metode pilihan untuk mengukur
massa tulang karena cepat, tepat dan menyebabkan tingkat paparan radiasi
rendah. Densitometri tulang mendeteksi kehilangan massa tulang kurang dari
5%, sedangkan sistem sinar-x mendeteksi kerugian 30 sampai 50%. Penafsiran
DEXA pada anak merupakan tantangan karena perubahan ukuran tulang dan
geometri yang terjadi selama pertumbuhan dan perkembangannya. Penafsiran
yang benar terhadap data harus memperhitungkan kematangan kerangka,
perkembangan pubertas, asal etnis, berat dan tinggi pasien. Massa tulang
dicatat dalam hal kandungan mineral tulang (BMC, gram) dan kepadatan
mineral tulang (BMD, g / cm2), dan keduanya dapat dipengaruhi oleh ukuran
tulang. Meski BMD disesuaikan dengan area tulang yang dipindai, ini tidak
memperbaiki perbedaan ketebalan tulang. Dengan demikian, kepadatan
sebenarnya dilebih-lebihkan dalam tulang besar dan diremehkan pada tulang-
tulang kecil. Untuk menghindari masalah ini sejumlah model matematis yang
berbeda telah dikembangkan untuk memperkirakan volume tulang (g / cm3).
Untuk memperbaiki kandungan mineral tulang seluruh tubuh untuk ukuran
tulang, Molgaard dkk. Telah menyarankan untuk mengambil tinggi dan tulang
dari masing-masing individu. Meskipun tidak ada konsensus mengenai metode
terbaik untuk menyesuaikan ukuran tulang, umur skeletal dan perkembangan
pubertas harus dipertimbangkan saat menafsirkan studi densitometrik
pediatrik. Metode lain yang digunakan untuk mengukur BMD meliputi
kuantitatif komputerisasi tomografi (QCT) dan Ultrasound kuantitatif (QUS).
Tomografi terkomputerisasi kuantitatif mengukur BMD volumetrik, namun
pasien dikenai radiasi dosis tinggi, yang dapat diminimalkan dengan
menggunakan komputerisasi kuantitatif komputerisasi (pCTQ). USG kuantitatif
sering digunakan untuk menilai BMD kalkaneus dan falang. Ini adalah
pemeriksaan yang mudah dilakukan, dengan biaya rendah dan tidak melibatkan
radiasi. Namun, selama masa kanak-kanak, struktur makro tulang dari area
yang dievaluasi terus berubah, yang kompromi
Sensitivitas pemeriksaan ini.

Biochemical markers of bone remodeling

The biochemical markers of bone remodeling can be divided into markers of formation and
or reabsorption. These markers can be tested for in blood and urine. The results are difficult
to interpret, especially in children and adolescents, since they reflect the growth and
remodeling, which is intense at these ages. Average values and interindividual variation are
many times greater in children than in adults. Biochemical markers reach their maximum
values at the start of adolescence (Tanner stage II), diminishing after this phase, despite
continued gains in both size and mineral density of the bones. The wide variation in normal
values and the need to adjust for stage of pubertal development limit the value that markers
have in defining normal or abnormal bone remodeling. Furthermore, these are expensive
tests, of low specificity and sensitivity and are influenced by diet, circadian cycle and renal
function.
Penanda biokimia dari remodeling tulang dapat dibagi menjadi beberapa
spidol formasi dan atau reabsorpsi. Penanda ini dapat diuji dalam darah dan
air kencing. Hasilnya sulit untuk ditafsirkan, terutama pada anak-anak dan
remaja, karena mereka mencerminkan pertumbuhan dan pemodelan ulang, yang
sangat kuat pada usia ini. Nilai rata-rata dan variasi antarindividu
berkali-kali lebih besar pada anak dibandingkan orang dewasa. Penanda
biokimia mencapai nilai maksimum mereka pada awal masa remaja (Tanner tahap
II), berkurang setelah fase ini, meskipun mendapat keuntungan lanjutan baik
pada kepadatan ukuran dan mineral tulang. Variasi yang lebar normal
Nilai dan kebutuhan untuk menyesuaikan tahap perkembangan pubertas
membatasi nilai yang dimiliki penanda dalam menentukan remodeling tulang
normal atau abnormal. Selanjutnya, ini adalah tes mahal, spesifisitas dan
sensitivitas rendah dan dipengaruhi oleh diet, siklus sirkadian dan fungsi
ginjal.

Markers of bone formation include bone-specific alkaline phosphatase (BALP), an enzyme

produced only by osteoblasts and essential to bone mineralization. Osteocalcine (OC) is a
small collagen protein with uncertain function, synthesized by osteoblasts to be incorporated
into the bone matrix. A fraction of recently liberated OC is liberated into circulation and can
be measured by radioimmunoassay. Osteocalcine has been show to follow a circadian rhythm
and to reflect bone formation. The carboxyl-terminal and amino-terminal propeptides of type
I procollagen are liberated by the type I collagen molecule before incorporation into the
matrix collagen fibrils. They can be measured in serum by immunoassay, but they may also
reflect collagen metabolism in other locations, such as the skin. The non-collagen proteins
produced by osteoblasts (OC and BALP) are the most sensitive and specific bone formation
markers. Useful bone reabsorption markers are generally those that are products of collagen
degradation. The type I collagen cross linked N-telopeptide (NTx) and cross linked
Ctelopeptide (CTx) are products of type I collagen degradation and can be measured by
immunoassay in the urine and nowadays in serum as well. Pyridinoline and
deoxypyridinoline (DPD) are cross linked covalents found in type I collagen, liberated during
bone reabsorption, metabolized and found in urine either freely existing or bonded to
peptides. They are more sensitive markers of bone reabsorption than hydroxyproline (the
classical urinary reabsorption marker). Tartrate resistant acidic phosphate (TRAP) is an
enzyme liberated by osteoclasts, but also derived from erythrocytes. Its usefulness is limited
because it is not stable in serum, even when frozen. Currently, the best markers for bone
reabsorption definition are DPD and NTx or CTx.
Penanda pembentukan tulang termasuk fosfatase alkali spesifik tulang
(BALP), enzim yang diproduksi hanya oleh osteoblas dan penting untuk
mineralisasi tulang. Osteocalcine (OC) adalah protein kolagen kecil dengan
fungsi tidak pasti, disintesis oleh osteoblas untuk dimasukkan ke dalam
matriks tulang. Sebagian kecil OC yang baru dibebaskan terbebaskan dalam
sirkulasi dan dapat diukur dengan radioimmunoassay. Osteocalcine telah
ditunjukkan untuk mengikuti ritme sirkadian dan untuk mencerminkan
pembentukan tulang. Propertida tipe karboksil-terminal dan amino-terminal
Saya procollagen dibebaskan oleh molekul kolagen tipe I sebelum digabungkan
ke dalam fibril kolagen matriks. Mereka dapat diukur dalam serum dengan
immunoassay, tetapi juga dapat mencerminkan metabolisme kolagen di lokasi
lain, seperti kulit. Protein non-kolagen yang diproduksi oleh osteoblas (OC
dan BALP) adalah penanda pembentukan tulang yang paling sensitif dan
spesifik. Penanda reabsorpsi tulang yang berguna pada umumnya adalah produk
degradasi kolagen. Kolagen tipe I yang menghubungkan N-telopeptida (NTx)
dan CNAopeptida silang (CTX) adalah produk degradasi kolagen tipe I dan
dapat diukur dengan immunoassay dalam urin dan sekarang juga dalam serum.
Pyridinoline dan deoxypyridinoline (DPD) adalah kovalen silang yang
ditemukan pada kolagen tipe I, terbebas selama reabsorpsi tulang,
dimetabolisme dan ditemukan dalam urin yang bebas atau terikat pada
peptida. Mereka adalah tanda reabsorpsi tulang yang lebih sensitif daripada
hidroksiprolin (marker reabsorpsi urin klasik). Tartrat tahan asam fosfat
(TRAP) adalah enzim yang dibebaskan oleh osteoklas, tetapi juga berasal
dari eritrosit. Kegunaannya terbatas karena tidak stabil dalam serum,
bahkan saat dibekukan. Saat ini, penanda terbaik untuk definisi reabsorpsi
tulang adalah DPD dan NTx atau CTx.

Diagnostic
Bone densitometry
Any child with a history of fragility fractures should be assessed with bone densitometry. A
significant family history of recurrent fractures is suggestive of an underlying inherited
condition, and in these cases it is often helpful to study first-degree family members. An
expert panel has recently recommended densitometry for children with a history of clinically
significant fractures, defined as a long bone fracture of the lower extremities, a vertebral
compression fracture, or two or more long-bone fractures of the upper extremities (18). The
decision to screen becomes less clear when evaluating children with multiple traumarelated
fractures. For most patients, assessment is made on an individual basis, taking into
consideration severity and number of fractures, along with other risk factors. Multiple
methods are available for assessing bone density including DXA, quantitative computed
tomography (QCT), and quantitative ultrasound. Plain radiographs are not recommended for
quantification of BMD but are useful for identifying fractures, deformity, skeletal dysplasias,
rickets, and sclerosing bone disorders. DXA is currently the preferred method, given its wide
availability, rapid scanning time, and low radiation. The sites typically studied are the
postero-anterior lumbar spine, proximal femur, distal radius, and total body. The postero-
anterior spine and TBLH (total body without the head) for evaluation and monitoring because
they are the most reproducible and accurate sites measured by DXA. In children with
impaired mobility, scans of the distal femur may be more informative (21). A comprehensive
pediatric reference database for Hologic densitometers is available it is important that only
normative databases specific to the brand of densitometer be used for interpretation. Z-scores
should be calculated as SD scores compared with age-, sex-, and ethnicity-matched controls.
The diagnosis of low BMD in a child should never be made on the basis of T-score (SD score
compared with young adults at peak bone mass) (Fig. 2). This error has led to the
overdiagnosis of low BMD in children (23). DXA is a two-dimensional technology
measuring areal BMD, calculated as the bone mineral content divided by the area of interest,
reported in grams per square centimeter. The inability of DXA to measure the true
threedimensional volume of the bone has important implications because areal BMD will be
decreased in smaller bones and increased in larger bones. A patient with short stature may
therefore have abnormally low areal BMD compared with the average population despite
normal true volumetricBMD(24). There are several methods that may be applied to correct
areal BMD for body size, using mathematical models (25, 26) and adjusting TBLH or body
composition (27). Interpretation of DXA scans should include consideration of not only
height but also bone age and pubertal status. Lean body mass has been shown to correlate
with BMD(28 –30), which may have particular significance in patients with complications of
chronic disease leading to relative sarcopenia. Methods have been developed to estimate the
effects of lean body mass on BMD (29, 30); however, these adjustments may be problematic
in children with fluctuating body composition, acute exacerbations of underlying disease,
and/or their treatment. In addition, local structural changes such as vertebral fractures,
osteophytes, and arterial calcifications can lead to spuriously elevated BMD measurements.
Quantitative ultrasound can be used to assess BMD; however, diagnostic significance has not
been well-established, and it is not recommended. QCT of the spine has the advantage over
DXA in that it can distinguish between trabecular and cortical bone and can determine true
threedimensional volumetric BMD. Unfortunately, expense, availability, and high radiation
exposure makes axial QCT impractical for routine clinical use. QCT can be performed on the
peripheral skeleton using much less radiation; however, this technique is confounded by the
continually changing size and shape of the growing skeleto. There are multiple emerging
modalities, used primarily in research, such as high-resolution peripheral QCT, high-
resolution magnetic resonance imaging, and micro-computed tomography, which surmount
many of the limitations of DXA and have the potential for future clinical use. The clinical
definition of osteoporosis includes low BMD, increased bone fragility with associated
changes in bony microarchitecture, and an increased risk of fracture. There is evidence in
adults that low BMD is predictive of increased fracture risk, and a BMDT-score less than -2.5
SD is suggestive of osteoporosis in adults (35). The clinical relevance of low BMD in
children has not been well-established, although there are retrospective data that suggest an
increased fracture risk when the Z-score is less than -2 and one prospective study reporting an
89% increase in fracture risk for every SD decrease in size adjusted BMD. However, spine
BMD by DXA may overlook clinically apparent osteoporosis, as was recently described in a
child with multiple thoracic compression fractures despite a normal lumbar spine Z-score
(37). Concurrent vertebral fracture assessment done by DXA has lower radiation than plain
radiographs and is useful in adults; unfortunately, the current software is inadequate for
pediatric use (38). The diagnosis and management of osteoporosis in the pediatric patient
must therefore be based on a combination of clinical and radiographic findings, rather than
relying upon bone densitometry alone. The International Society for Clinical Densitometry
recently updated its official position on DXA evaluation in children and adolescents,
recommending that the “diagnosis of osteoporosis requires the presence of both a clinically
significant fracture history and low bone mineral content or bone mineral density”.
Conventional densitometry methods provide information about bone mass. However, bone
strength is dependent not only on bone mass and density but also the structural properties that
resist bending and fracture. Mathematical models exist that use DXA and QCT to estimate
measurements of bone strength. Further research into this area may yield applications in the
clinical setting.
QCT results demonstrated that bone mineral density (BMD) was reduced in both trabecular/lumbar
and cortical/femoral bone in the two compartments, respectively