Transcript Osteoporosis in Children

Osteoporosis in Children
Nasir A.M. Al-Jurayyan
Professor of Paediatrics and
Consultant Paediatric Endocrinologist
College of Medicine and King Khalid University Hospital
King Saud University, Riyadh
Bone consists of a collagen matrix into which
calcium, in the form of hydroxy apatite, is
deposited.
The
accumulation
and
maintenance of the substance of bone is the
result of a continuous process of formation,
predominantly mediated by osteoblast, and
resorption, facilitated by osteoclast. During
childhood
and
adolescence,
formation
predominates, leading to a net increase in
bone mass and size, with infancy and
adolescence being periods of particularly
rapid formation.
Osteoporosis
is
defined
as
a
systematic disease characterized by
low bone mass and microarchictectural
deterioration of bone tissue with a
consequent increase in bone fragility
and susceptibility to fractures, while
Rickets and osteomalacia are due to
failure of bone mineralization.
Osteoporosis remains
the
most
common metabolic bone disorder in
adults. However, there is now
increasing evidence that the roots of
osteoporosis lie in childhood.
Peak bone mass is achieved shortly
after completion of puberty and
normally remains stable until the 3rd
decade of life when age-related
(involutional) bone loss begins with a
steady decline (about 1% per year).
Failure to achieve optimal peak bone
mass represents a significant and
preventable risk factor for osteoporosis
in later years.
Osteoporosis that is symptomatic
during childhood is currently emerging
as a newly recognized problem among
specific at risk populations.

Bone Mineral Density Determinants
– Intrinsic (unmodifiable) factors (70-80%)
 Gender
 Ethnicity
 Family
Background
Males achieve a higher peak bone
mass, and because of both larger bone
size and slower decline in sex steroid
levels, aging men have a lower
incidence of osteoporotic fractures
than women.
Boot et al JCEM 1997
Kelly et al J Bone Mineral Res

Bone Mineral Density Determinants
– Intrinsic (unmodifiable) factors (70-80%)
 Gender
 Ethnicity
 Family
Background
Osteoporosis and fracture risk is lower
among African-Americans, both males
and females, due to higher bone mass
relative to their peers in other ethnic
groups.
Bachrach et al JCEM 1999
Bone mineral density (BMD) in Saudi
children, adolescents and adults is low
compared to Caucasian Americans.
*
El Desouki M Saudi Med J 1999
* El Desouki M Saudi Med J 1995

Bone Mineral Density Determinants
– Intrinsic (unmodifiable) factors (70-80%)
 Gender
 Ethnicity
 Family
Background


There is a strong familial component to
bone mineral density in adults, for example;
maternal bone mass is a strong predictor of
BMD in both prepubertal boys and girls, and
twins are strongly concordant for BMD.
A specific genetic marker?
* Jones G and Nguyen TU J Bone Miner Res 2000
* Seeman et al Am J Physiol 1996

Bone Mineral Density Determinants
– Extrinsic (modifiable) factors
 Diet
 Lifestyle habits
 Hormonal milieu
 Illness
 Medications
Nutritional Rickets and Osteomalacia in
Saudi school children and adolescents
Al-Jurayyan et al Saudi Med J 2002
Are Saudis at risk of developing
Vitamin D deficiency?
Sedrani SH. Saudi Med J 1986

Long-term-adult presentation
v.s.

Acute-Pediatric-Presentation

Acute Pediatric Presentation
– Primary Risk Factors

Chronic illness

Immobility

Medication
Conditions with Impaired Bone Mineral Density
Illness
Treatment
Osteogenesis Imperfection
Malignancy
GIT Deficiency
Cortisol Excess
Hypogonadism
Anorexia Nervosa
Hyperthyroidism
Hyperparathyroidism
Gastrointestinal
CNS/Neuromuscular
Glucocorticoids
Immuno suppressants
Irradiation
Anti convulsant
Evaluation and Treatment of
Osteoporosis in Children

Information
– History of risk Factors
– Physical Examination
– Critical Interpretation of DEXA data
– Other Laboratory Studies

Decision
– Risk v.s. Benefit
– Observation or Treatment
Evaluation of the
Osteoporotic Patient

History
– Fracture history-early fracture suggest genetic
abnormality – OI
– History of underlying chronic illness – patient at
risk?
– Dietary history – Calvit D intake
– Medication history

glucocorticoid, anti convulsant
– Activity history

Immobility / wt bearing
Evaluation of the
Osteoporotic Patient

Physical Examination
– Growth pattern

Disease or treatment affecting growth

Evidence for collagen disease

Cushingoid features

Scoliosis
Evaluation of the
Osteoporotic Patient


Laboratory evaluation
Ca / P / Alk phos
– Disorders of calcium metabolism

Intact PTH, Vit D metabolites
– Hypoparathyroidism
– Vitamin D deficiency



Free T4, TSH – hyperthyroidism
Urine Calcr - hypercalciuria
Urine amino acid
– Lysine metabolites

Skull x-ray for wormian bones
– OI



Spine films – vertebral #
Skin biopsy or DNA – OI
Bone metabolism markers?

Bone metabolism markers (such as AP,
osteocalcin, hydroxyproline) in serum
or urine are inferior to radiologic BMD
measurements
– Diurnal variation
– Influenced by puberty
– Limited pediatric reference

Range
De Ridder et al. Curr Opin Pediatr 1998
Evaluation of the
Osteoporotic patient

Determination of BMD
– Screening at risk patients
– Patients with fractures with minimal
trauma
– Osteopenia on plain film in an individual
with one or more risk factor



Whole body – insensitive
Lumbar spine – glucocorticoids
Hip – non – wt - bearing
The DEXA Alphabet




BMC – bone mineral content – g
BMD – bone mineral density – g/cm2
BMAD – bone mineral areal density = BMD
BMDvol – bone mineral volumetric density – g/cm3
BMD X [4/( x L2-L4 width)]
T-score – SDS score compared to adult gender-matched peak bone mass
(25, 35, 45 yo)
*T = -2 means density is 2 SDS below the mean for peak BMD
Z-score – SDS score compared to age- and gender-matched bone mass
Z = -2 means density is 2 SDS below the mean for age matched BMD
Calculating and Correcting
Z-Scores

DEXA values must be analyzed in relation
to age and gender normal values for the
machine and model
– Machine determined Z-score (makers data base)
– Calculation of Z-score based on published data
– Then correction of Z-score for:

Shortness
– Height age norms
– Volumetric correction

Pubertal delay
– Bone age norms
Choice of the “right”
Z-score
?
Diagnosing Pediatric
Osteoporosis

Barriers:
– Lack of diagnostic criteria

What BMD is associated with increased fracture risk?
– Lack of adequate normative data by age, gender,
race
– Lack of interchangeability between data from
different DEXA machines
– Antifact may be introduced by variation in height
and puberty.
Treatment of the Osteoporotic
Patients

Barriers
– No standard definition
– No consensus on the degree of BMD
impairment that places a child at risk
– No large, well controlled studies assessing
safety and efficacy
Treatment of the
Osteoporotic Child

A modest proposal
– Z-score > -1.5 and no fractures
Optimize Ca and Vit D
(? 800 iu/d)
 Increase activity – wt bearing
 Repeat DEXA in 6 m.
 Consider

– Pubertal v.s. prepubertal on goingRx v.s. D/C.
Treatment of the
Osteoporotic Child

A modest proposal
– Z-score < -1.5 and/or active
fracturing
 Optimize
Ca / Vit D
 Pharmacological options
– Correct known abn.
– GH↓ - GH -= Rx
– Hyperthyroidism – Antithyroid medication
– Biphosphonates
Treatment of the
Osteoporotic Child

Bisphosphonate options
– Alendronate (Fosamax)


Daily oral medication with GI Irritation
No data in pediatric patients
– Pamidronate (Arredia)




Most highly studied of the bisphophonates in children
Treatment of OI based on Paget disease in adults – 3 day
infusion every 2-3 months (0.25 – 1 mg/kg/day)
TCH – 3hr IV infusion every 3 months (30 – 45 mg/day)
Well-tolerated with minimal side effects (fever)
– Risedronate (Actonel)


New oral agent - ? Better tolerated
No data in pediatric patients
Prevention of Osteoporosis



“Optimizing Peak Bone Mass”
Most important – Pick the right
parents
Regular weight-bearing activity
Well-balanced diet
– Adequate calcium
– Adequate Vitamin D

Health life habits
– E.g. avoiding smoking
Summary




The prevalence, morbidity and mortality of
adult osteoporosis continues to grow
The roots of osteoporosis begin in childhood
Optimization of bone density accretion
during childhood can be assumed to have
long-term benefits
Osteoporosis is also a symptomatic disease
of childhood in the setting of chronic illness
and its treatment
Symptomatic Pediatric
Osteoporosis






A previously under-recognized problem, with
increasing prevalence
Well-defined high-risk populations
Significant short-term morbidity promotes a cycle of
disability
Long-term consequences likely, but not studied
Effective, well-tolerated treatment options are now
available
Clinicians should actively identify at-risk patients,
evaluate bone density, and consider treatment.