Calcium, Parathyroid, Bone Flashcards
iCa - what affects it
Decreased by:
Excess heparin
AlkaLOWsis
Increased by:
Acidosis
Longer storage/air exposure/higher temp
Prolonged tourniquet, forearm exercise
how does Mg affect PTH?
Hypo – decreases PTH secretion/action
Hyper – suppresses PTH secretion
PTH action?
Kidney: increase 1,25OH VitD production
->Increase Ca
Bone: increased bone turnover (osteoclast)
1,25OH Vit D action?
Gut: increases intestinal Ca absorption
Parathyroid: Feeds back to decrease PTH production
how does PTH affect kidneys and Ca?
increases distal tubular Ca reabsorption
what meds affect renal Ca excretion?
corticosteroids: increase Ca excretion
furosemide: increase Ca excretion
thiazide diuretics decrease Ca excretion
what is RANK
Receptor activator of nuclear factor kappa-B
osteoclasts
- function
- regulated by
bone resorption
RANK,
RANK ligand and
osteoprotegerin (OPG)
what happens when PTH acts on the PTH-R
PTH-R expresses:
more RANK-L
less OPG
This leads to more osteoclast action and more bone turnover
Hyper Ca DDX
Bone resorption:
- hyperPTH
– primary, MEN, familial isolated
- thyrotoxicosis
- vit D intoxication
- hypervitaminosis A
- immobilization
High Ca intake
- High Ca intakes for phosphate binding in renal failure
- milk alkali syndrome
- vitamin D intoxication
Other:
- subcutaneous fat necrosis
- malignancy (osteolytic mets, PTHrP)
- Williams syndrome
- Familial hypocaliuric hypercalcemia
- Meds: thiazides, lithium, theophylline
- Adrenal insufficiency
- pheochromocytoma
- hypophosphatasia
- rhabdomyolysis
- distal RTA
- Excess PTHrP (ie. tumour induced)
- hyperthyroidism
HyperCa in Neonates - DDx
- Excessive intake of calcium or Vit D’
- Exogenous
- Milk-alkali
- Granulomatous diseases – ectopic production of calcitriol - Phosphate depletion
- SC fat necrosis, Granulomatous disease (1-alpha hydroxylase)
- Williams syndrome
- Endocrinopathies:
- primary adrenal insufficiency
- severe hypothyroidism, or hyperthyroidism - Malignancy
- lytic bone lesions or PTHrP - Meds:
- thiazides, lithium, Vit A ,Ca, alkali etc. - Genetics
- Other:
- Immobilization
- Persistent PTHrP
Maternal hypoparathyroidism
Maternal pseudohypoparathyroidism
Genetic causes of HyperCa in neonates
- CYP24A1
- Jansen metaphyseal chondroplasia (activating mutation of PTH-R)
- LCT: Congenital lactase and other disaccharide deficiencies (2/2 increased intestinal absorption of Ca promoted by the disaccharides)
- Infantile hypophosphatasia (TNSALP: mutation in AlkPhos)
- Mucolipidosis type II
- Blue diaper syndrome
a. defect in absorption of tryptophan, ass/w hypercalcemia and nephrocalcinosis, pathogenesis unclear - Antenatal Bartter syndrome type 1 (SLC12A1) and type 2 (KCNJ1)
- Distal RTA
Familial Hypocalciuric Hypercalcemia
- gene
- labs
Due to dominantly inherited INACTIVATING mutation in the CaSR
Benign elevation in Ca
PTH normal to slightly high
HyperCa management
- fluid administration, restoration of intravascular volume
** cardiac monitoring - loop diuretcs
- glucocorticosteroids
- calcitonin
- bisphosphonates
- dialysis
- dietary management
how do glucocorticoids decrease Ca
- decrease intestinal Ca absorption
- decrease 1,25OHD production by activated mononuclear cells in patients w granulomatous disease or lymphoma
how does calcitonin work?
- inhibits bone resorption by interfering with osteoclast function
- tachyphylaxis
how do bisphosphonates work?
potent inhibition of bone resorption by interfering with osteoclast recruitment and function
hungry bone syndrome
Severe hypocalcemia (due to sudden removal of PTH effect on osteoclast bone resorption)
Hypophos
HypoMg
High ALP
cinacalcet
Stimulates the CaSR
Binds to transmembrane region of CaSR causing a structural change - increases the sensitivity thereby, concomitantly lowering parathyroid hormone (PTH), serum calcium, and serum phosphorus levels, preventing progressive bone disease
Hypophosphatasia
- what is it
- presentation
Inherited deficiency of ALP
Rickets like bone disease and craniosynostosis
Hypocalcemia Sx in neonate
neuromuscular hyperexcitability:
irritability, hyperacusis, jitteriness, tremulousness, facial spasms, tetany, laryngospasm, and focal or generalized sei- zures
Nonspecific symptoms, such as apnea, tachycardia, cyanosis, emesis, and feeding problems may also occur.
Acute Hypocalcemia Sx
Neuromuscular
- Perioral or extremity paresthesias
- Muscle cramps, twitching and weakness
- Smooth muscle spasms (potentially causing biliary and intestinal cramps, dysphagia, premature birth, and detrusor muscle dysfunction).
- Latent tetany with + Chvostek and Trousseau
- Overt tetany, with carpopedal spasms, laryngospasm, bronchospasm
Neuropsychiatric
- Irritability, anxiety, depression, psychosis, mental confusion
Cardiovascular
- Rate-corrected QT interval (QTc) prolongation on EKG
- Bradycardia or ventricular arrhythmias
- Decrease in myocardial contractility, hypotension and heart failure
Ocular
- Papilledema
Chvostek’s sign
Percussing the facial nerve approximately 2 cm anterior to the ear, causes contraction of the ipsilateral facial muscles.
Trousseau’s sign
Inflate the BP cuff to approximately 20–30 mmHg above systolic for 3 minutes.
Characterized by carpal spasms, with adduction of the thumb, flexion of the metacarpophalangeal joint, extension of the interphalangeal joints, and flexion of the wrist
Chronic hypocalcemia sx
Neuropsychiatric Abnormalities
- Cognitive deficits and or dementia
- Extrapyramidal symptoms and signs that resemble Parkinson’s disease or chorea
- Calcification of basal ganglia (detected with greater sensitivity by CT scans than ordinary skull x-rays)
- Greater susceptibility to dystonic reactions induced by phenothiazines
Ocular
- Subcapsular cataracts
Dental
- Abnormal dentition
Ectodermal
- Dry skin
Neonatal hypocalcemia Ddx
maternal diabetes
maternal hyperparathyroidism
Vitamin D deficiency
High intake of alkali or magnesium sulfate
Use of anticonvulsants
prematurity/LBW
birth trauma/asphyxia
sepsis, toxemia
hypoparathyroidism (DiGeorge)
hypomagnesemia
Acute/chronic renal failure
excessive phos intake
inadequate calcium intake
vitamin D deficiency
hyperphosphatemia
pseudohypoparathyroidism
Vitamin D def or resistance
Osteopetrosis type II
mgmt hypocalcemia
IV Ca gluconate
Bolus first
Indications: sx’atic, QTc interval prolonged
EKG/cardiac monitor to assess QT interval. Observe for stridor.
Decrease phosphate in TPN if applicable
GNAS activating mutation
GNAS inactivating mutation
GNAS activating mutation = McCune Albright
GNAS inactivating mutation = Albright hereditary osteodystrophy
Pseudohypoparathyroidism
types
PHP1A – Albright hereditary osteodystrophy (AHO)
PHP1B – isolated resistance to PTH
PseudoPHP
Somatic phenotype of AHO without disorder of calcium metabolism
where is the GNAS gene imprinted
paternal allele imprinted in the kidney (ie silenced)
what is the AHO phenotype
short stature
round facies
obesity
brachydactyly
developmental delay
dental hypoplasia
basal ganglia calcifications
decreased bone density
subcutaneous calcifications
lenticular opacities
strabismus
cognitive impairment
PHP type 1a
- inheritance
- features
- AD
- Resistance to PTH
-> hypocalcemia, hyperphosphatemia, elevated PTH
-> impaired urinary excretion of cyclic AMP and phosphate after administration of exogenous PTH - Resistance to TSH, gonadotropins, and GHRH
- AHO
- Less commonly reproductive abnormalities –> oligomenorrhea and infertility due to primary hypogonadism
PHP type 1b
- inheritance
- features
- Sporadic
– Only in the offspring of obligate female carriers in whom loss of maternal GNAS expression is present in the renal proximal tubule, resulting in selective proximal renal tubular resistance to PTH
–Skeletal expression of both maternal and paternal GNAS is intact and hence bone formation is normal
Resistance to PTH
–Linked to GNAS locus but not due to mutations in the coding region of GNAS
–So no somatic phenotype
–Either due to improving or deletion of a methylated region on the GNAS locus (key regulator of the levels of GNAS transcription)
Can have resistance to TSH as well
Progressive osseous heteroplasia
- Rare disorder involves the GNAS locus
- Ectopic bone formation more severe than PHP1A
- Begins in early childhood with ectopic bone forming in the dermis, muscles, and connective tissues
- Can also have short stature, brachydactyly
- No calcium or PTH abnormalities
inherited defects of CaSR
Inactivating – High PTH & high calcium
1. Neonatal severe hyperparathyroidism (AR)
2. Familial Benign Hypocalciuric hypercalcemia(AD)
Activating – Low PTH & low calcium
1. AD Hypocalcemic hypercalciuria
acquired defects of CaSR
Autoimmune hypocalciuric hypercalcemia (hyperparathyroidism)
- Blocking Ab vs. CaSR
- Acts like inactivating mutation
Autoimmune acquired hypoparathyroidism
- Stimulating Ab vs. CaSR
- Acts like activating mutation
what kin d of receptor is Vit D
nuclear steroid hormone receptor
vitamin D metabolism
skin/diet VitD
Liver 25 hydroxylase
makes 25OH Vit D
Kidney 1alpha hydroxylase
makes 1,25 (OH)2 Vit D
Abnormal mineralization of bone and cartilage
- names in growing children and adults
Osteomalacia – bone defect occurring after epiphyseal plates have closed
Rickets – occurs in growing bone (i.e. in children)
Definition of rickets
1) Deficient mineralization at the growth plate
+ 2) architectural disruption of this structure.
Rickets DDx
- Vit D deficiency from lack of sun or dietary insufficiency
- 25 hydroxylase deficiency in the liver
- 1,25 hydroxylase deficiency in the kidney
— Chronic renal failure
— Low serum Ca
— High PTH
— Low 1,25 Vit D
— Normal 25 Vit D - Vit D receptor deficiency
— Also assoc to alopecia - Renal
Rickets features
- Rachitic rosary (prominence of costochondral junctions)
- Frontal bossing
- Delayed closure of fontanelles
- Bowing of legs
- Craniotabes
- Delayed eruption of teeth with poor enamel formation, pitting
- Harrison’s groove
- Pectus carinatum
- Scoliosis and kyphosis
- Flaring of the metaphyses of the long bones
- Poor growth, short stature
- Muscle hypotonia pronounced potbelly and waddling gait
- Pathologic fracture
Rickets X-ray
**Widening of growth plate (epiphyseal plate)
(proliferation of uncalcified cartilage and osteoid)
**Irregularity of the epiphyseal-metaphyseal junctions
(which gives the swelling along costochondral junctions = rachitic rosary)
** Early signs
- Metaphyseal cupping, splaying and fraying (vs. sharp demarcation and slightly convexshape)
- Osteopenia
- Bowing of long bones (if wt bearing)
- Pseudofractures (= Looser’s zones or Milkman’s fractures)
—-unhealed microfractures at points of stress or at entry point of blood vessels into bone
what does FGF23 do
will increase urinary phos excretion
Decrease 1,25 Vit D
signs of low phosphate
Muscle weakness/dysfunction/fatigue
Neuro sx if acute hypophos (parathesias, altered mental status, seizure)
Hypophosphatemia Ddx
- Renal phosphate wasting (main cause)
- Acute phosphate redistribution
= Refeeding syndrome - High PTH
= PTH inhibits phosphate reabsorption in proximal renal tubule - Decreased GI uptake / intestinal absorption
=Starvation, e.g. AN
=Vitamin D deficiency
=Malabsorption
=Inhibition of phosphate absorption (eg, antacids containing aluminum or magnesium, niacin)
=Chronic alcoholism
=Steatorrhea and chronic diarrhea
=Vitamin D deficiency or resistance (VDDR1: mutation in 1-alpha-hydroxylase) - Renal losses / increased urinary excretion
= Hyperparathyroidism – primary and secondary
= Hypophosphatemic rickets (X-linked and AD)
= Vit D Def or resistance
= RTA (fanconi)
= Diuretic therapy
= Hypomagnesemia
= Aldosteronism
= HHRH : Hereditary hypophosphatemic rickets with hypercalciuria (LOF mutations in Na-Pi IIc)
= Oncogenic osteomalacia - Intracellular shifts / internal redistribution
= Alkalosis (metab or resp)
= Increased insulin secretion (particularly refeeding)
= Hungry bone syndrome
= Administration of corticosteroids, epi, lactate, glucose, insulin
= Recovery from hypothermia - Misc
= Acute gout
= Hypokalemia
= Carcinoma – tumor induced osteomalacia
= DKA
= Alcohol withdrawal
FGF23 mediated hypophosphatemia
- x-linked hypophosphatemic rickets
- AD hypophosphatemic rickets
- AR hypophosphatemic rickets
- McCune Albright Syndrome
- Tumour induced (oncogenic osteomalacia)
x-linked hypophosphatemic rickets
- treatment
- phosphate 20-40mg/kg/day div 4-6 times per day
- calcitriol 20-30ng/kg/day div BID
Burosumab (anti-FGF23 antibody) -decreases phosphate loss
what are renal hypophosphatemia causes (FGF23 independent)
- Fanconi syndrome
- hereditary hypophosphatemic rickets w hypercalciuria
- hyperparathyroidism
how to calculate phosphate loss
TRP = tubular reabsorption of phosphate
TRP% = 1- [(urinary phosXserum Cr) / (serum phosxurinary creatinine) x 100
to get normal for age, use Bijvoet nomogram
higher when younger, lower when older
hyperphosphatemia ddx
- acute phosphate load
—cell lysis (tumour lysis, rhabdo, crush injuries, hemolytic anemia) or exogenous phosphate administration (Fleets, high phosphate formulas in neonates) - acute extracellular phosphate shift
- kidney
- increased tubular phosphate reabsorption
–hypoparathyroidism, acromegaly, vit D toxicity, bisphosphonate use, tumoral calcinosis
Hyperphosphatemia Treatment
Acute
Often accompanied by hyperCa
Dialysis
Chronic
Low phosphate diet
Phosphate binding agents
what is used for BMD
Z scores (standard deviation for age/sex)
Osteoporosis Definition
EITHER
Vertebral compression fracture (in absence of local disease or high energy trauma)
OR
Clinically significant fracture (2 or more long bone # by age 10; 3 or more by age 19)
AND
low BMD
Meds that can cause osteoporosis
Glucocorticoids
GnRH agonist
Anticonvulsants
Heparin
Immunosuppressants: MTX, Cyclosporine A
Lithium
Antiretrovirals
Diuretics
L-thyroxine suppressive therapy
Low BMD Tx
Calcitonin (reduces bone resorption)
Tachyphylaxis
Bisphosphonates
IV
PO
how do bisphosphonates work
- synthetic, stable pyrophosphate analogues
- bind to hydroxyapatite crystals in bone
- inhibit osteoclast-mediated bone resorption
pediatric uses of bisphosphonates
- hypercalcemia
- osteogenesis imperfecta
- immobilization osteoporosis
- Duchenne muscular dystrophy
- idiopathic juvenile osteoporosis
- juvenile Paget’s (idiopathic hyperphosphatasia)
- juvenile arthritis
- cerebral palsy
- fibrous dysplasia
side effects of bisphosphonates
Acute
- Fever
- Myalgia
- Abdominal pain, dyspepsia
- Vomiting
- Hypocalcemia, hypophosphatemia
- Bone pain
- Pain at infusion site
- Headache
- Allergic reaction
*Acute phase reaction usually only after 1st dose
Chronic
1. Inflammatory disorders of the eye
2. Osteonecrosis of the jaw (in the elderly)
3. Induced osteopetrosis
How steroids cause osteoporosis
- inhibition of osteoblastogenesis
- increase in the rate of apoptosis of the osteoblast and osteocyte ◊ decrease in the rate of bone matrix formation and microfracture repair
- enhanced osteoclastogenesis
- decrease in the rate of apoptosis of the osteoclast ◊ permitting prolonged and excessive bone resorption
- decreased intestinal calcium absorption
how to treat acute hypocalcemia
IV calcium bolus - recommended dose of elemental calcium is 5 to 7 mg/kg
10% calcium gluconate 1ml/kg (or 0.6)
10% CaCl 0.2 mL/kg (ONLY CENTRAL)
what happens if you give Ca with phos or K
it precipitates
meds for hypocalcemia chronic
aims for labs
- Calcium: 50-75 mg/kg/day elemental calcium in divided doses
- Calcitriol: Start 20-60 ng/kg/day in 2-4 doses OR start at 0.25 mcg/day and titrate up to effect
AIMS:
calcium low normal
phosphate high normal
what is the % Elemental Calcium by supplement
Calcium carbonate 40%;
citrate 21%;
gluconate 9%;
lactate 13%
HyperCa in older children
- Hyperparathyroidism (primary: sporadic, associated with MEN1, 2A)
- FHH (familial hypocalciuric hypercalcemia)
- Post-renal transplant
- Lithium
- Tertiary hyperparathyroidism (chronic renal failure)
- Humoral hypercalcemia of malignancy
- PTHrP (solid tumours, adult T-cell leukemia syndrome)
- Ectopic secretion of PTH (rare)
- Local osteolytic hypercalcemia (multiple myeloma, leukemia, lymphoma)
- Sarcoidosis/other granulomatous disease
- Thyrotoxicosis (hyperthyroid bone disease)
- Adrenal insufficiency
- Pheochromocytoma
- VIPoma
- Drug-induced (vitamin A intoxication, vit D intoxication, thiazide diuretics, lithium, milk-alkali syndrome, estrogens/androgens, tamoxifen (in BRCA))
- immobilization
- idiopathic hypercalcemia of infancy (not relevant here because older kid)
- subcutaneous fat necrosis
acquired problems with CaSR
-Autoimmune hypocalciuric hypercalcemia (in APS1) → anti CaSR which inhibit stimulation of CaSR by calcium and result in hyperparathyroidism
-Acquired autoimmune hypoparathyroidism - acquired antibodies against extracelular portion of CaSR
dose of pamidronate
pamidronate 0.5-2mg/kg over 4 hours
differentiating features between FHH and primary hyperparathyroidism
i) No findings on ultrasound
ii) Lower PTH
iii) Higher urinary calcium excretion
iv) AD family history
v) Hypercalcemia is present from young age (from birth if investigations are done)
vi) Elevated magnesium
What medication can modulate CaSR? How does it work?
i) Magnesium: binds to CaSR and causes reduced PTH secretion and lower calcium
ii) Cinacalcet: Can upregulate CaSR expression
Causes of osteoporosis
Chronic illness
a. Malignancy (leukemia, lymphoma)
b. Rheumatologic disorders
c. Anorexia nervosa
d. Cystic fibrosis
e. Inflammatory bowel disease
f. Renal disease
g. Transplantation
h. Other: primary biliary cirrhosis, cyanotic congenital heart disease, thalassemia, malabsorption syndromes, celiac disease, epidermolysis bullosa
Neuromuscular disorders
a. Cerebral palsy
b. Rett syndrome
c. Duchenne muscular dystrophy
d. Spina bifida
e. Spinal muscular atrophy
Endocrine and reproductive disorders
a. Disorders of puberty
b. Turner syndrome
c. Growth hormone deficiency
d. Hyperthyroidism
e. Hyperprolactinemia
f. Athletic amenorrhea
g. Cushing syndrome
h. Type 1 diabetes
Iatrogens
a. Glucocorticoids
b. Methotrexate
c. Cyclosporine
d. Heparin
e. Radiotherapy
f. GnRH agonist
g. Medroxyprogesterone acetate (long-term use)
h. L-Thyroxine suppressive therapy
i. Anticonvulsants
Inborn errors of metabolism
a. Lysinuric protein intolerance
b. Glycogen storage disease
c. Galactosemia
d. Gaucher disease
osteogenesis imperfecta
- what protein is implicated
- features of the protein that are important for normal function
type 1 collagen
most commonly caused by mutations in genes encoding the alpha-1 and alpha-2 chains of type I collagen or proteins involved in posttranslational modification of type I collagen
i. Has to form helix
ii. Helices have to form triple helix
features of osteogenesis imperfecta
i. Blue sclera
ii. Fractures of long bones
iii. Osteopenia
iv. Hearing loss
v. Bony deformities
vi. Wormian bones
vii. Triangular facies
viii. Abnormal skull formation
ix. Triangular face
x. Easybruising
xi. Wormian bones (small irregular bones along the cranial sutures)
how do bisphosphonates help in OI
i. Reduce fractures
ii. Reduce bone pain
iii. Increase mobility
iv. Reduce hypercalcemia
v. Prevent long bone deformities and scoliosis
vi. Decreased bone turnover
what are PTH mediated causes of rickets?
Vitamin D deficiency
Calcium deficiency
Disorders of vitamin D metabolism
• 1 alpha hydroxylase deficiency
• vitamin D receptor defect
PTH increased, increased renal excretion of phosphate
what causes of are FGF23 mediated rickets
X-linked hypophosphatemia (XLH)
Autosomal dominant hypophosphatemic rickets (ADHR)
Autosomal recessive hyophosphatemic rickets (ARHR-1)
Tumor-induced osteomalacia (TIO)
Osteoglophonic dysplasia (FGFR1)
Generalized arterial calcifications of infancy (ARHR-2)
Raine syndrome (ARHR-3)
Fibrous dysplasia
important factors for a healthy adolescent to attain peak bone mass
• Gonadal steroids (testosterone, estradiol)
• Weight bearing and resistance physical activity
• Adequate calcium intake (1300mg/day – for 9-18 y.o)
• Optimize vitamin D level
• Adequate nutrient and caloric intake
• Avoid smoking and alcohol
• Physical activity
• Race – African American females tend to achieve higher peak bone mass than white females
imaging in hyperparathyroidism
used only to differentiate an adenoma from hyperplasia.
The imaging techniques available include:
99T-sestamibi,
ultrasound,
CT,
or MRI.
In peds we mainly do ultrasound or 99T-sestamibi.
99T-sestamibi is more sensitive for adenoma so it preferred, but if there is hyperplasia of multiple glands it is hard to detect and ultrasound is better.
what are risk factors for hungry bone syndrome
high ALP,
parathyroid adenoma >5 cm,
very elevated calcium and PTH
the osteitis fibrosa cystica
what are the bone lesions in hyperparathyroidism?
Osteitis fibrosa cystica are the bone lesions seen in the phalanges and skull in hyperparathyroidism
what are RF for SCFN
mec aspiration, preeclampsia, maternal DM, therapeutic cooling
how long can nodules appear in SCFN
6 weeks
William syndrome Ca effects ?
High Ca
Low PTH
Low Vit D
elastin gene
what is craniosyostosis seen in
X-linked hypophosphatemic rickets
what are causes of Bone resorption
- hyperPTH
– primary, MEN, familial isolated - thyrotoxicosis
- vit D intoxication
- hypervitaminosis A
- immobilization
preferred site for DEXA in children
lumbar spine and total body
causes of Rickets
i. Nutritional - Vitamin D &/or Calcium deficiency
ii. Hypophosphatemic rickets
iii. Renal rickets (due to renal insufficiency)
acute hypoCa - what to watch for
laryngospasm
how does hypoMg cause hypocalcemia
inducing resistance to parathyroid hormone (PTH) and by diminishing its secretion
how does hypoMg cause hypocalcemia
inducing resistance to parathyroid hormone (PTH) and by diminishing its secretion
endocrinopathies that can cause hyperCa
- primary adrenal insufficiency
- severe hypothyroidism, or hyperthyroidism
what is Blomstrand chondroplasia
(PTHR1–lossoffunction mutation)
PTH resistance
Causes of hypoparathyroidism
CONGENITAL
1. Transient neonatal
a. delayed developmental maturation of parathyroid glands (resolves in first few wks of life)
b. Maternal hyperparathyroidism
- Dysgenesis/agenesis of the parathyroid glands
ex: DiGeorge syndrome (TBX1) – hypoplasia of the parathyroid glands - Insensitivity to PTH
a. Blomstrand chondroplasia(PTHR1–lossoffunction mutation) - PTH resistance
b. Pseudohypoparathyroidism - resistance
i. Type IA, IB, and IC
ii. Type II
iii. Pseudopseudohypoparathyroidism
c. Hypomagnesemia
d. Dyshormonogenesis
ACQUIRED
1. Autoimmune, APS type1 (AIRE1)
2. Activating Ab’s to the CaSR
3. Postsurgical
4. Radiation destruction
5. Infiltrative – excessive iron (hemochromatosis, thalassemia) or copper (Wilson) deposition, granulomatous or neoplastic invasion, amyloidosis,
sarcoidosis
6. Hypomagnesemia
Jansen’s metaphyseal dysplasia
activating mutation PTHR
5 factors for osteoporosis in DMD
1) reduced muscle tension on bone
2) steroids
3) delayed puberty
4) chronic inflammation (attempted repair of damaged muscle fibres)
5) immobility
Risk factors for metabolic bone disease of prematurity
- GA <28w
- BW <1500g
- TPN >4 weeks
- CLD
- long term diuretics
- NEC grade 2 or more
- fluid restriction
pathophys of MBD of prem
low Ca -> high PTH -> low phos -> decreased apoptosis -> hypertrophic chondrocytes
*low TRP
