Call Girls Service Bellary Road Just Call 7001305949 Enjoy College Girls Service
Osteomalcia1 1
1. Dr Praveen R Mishra (PG 2)
Dr Akash Bharti (PG 1)
2. CASE
• 33 year old Asian lady
• Presents with 3 /12 months history of generalised bony
pain
• PMH depression
• D/Hx sertraline
• P/Ex generalised bony tenderness
• Joints normal ROM, no inflammation
3. INVESTIGATIONS
• Hb 12.9 (11.5-16.5) Calcium 2.18 (2.2-2.6)
• WBC 4.7 (4.9-11.0) Phosphate 0.79 (0.85-1.45)
• Plt 253 (150-400) Albumin 39 (35-50)
• ESR 12 Alk Phos 172 (25-96)
• Clotting Normal Total protein 72 (60-80)
• Urea 4.2 (3.0-6.5) LFTs normal
• Creat 85 (35-120)
5. Bone cells
1. Osteoclasts
2. Osteoblasts
3. Osteocytes
Extracellular matrix
1. Organic : made up collagen, it forms 30-35% dry weight
2. Inorganic : primarily calcium and phosphorus especially hydroxyapatite , it
constitutes 60-65% of dry weight .
7. Osteomalacia is the softening of the bones caused by defective bone
mineralization
Osteomalacia in children is known as rickets, and because of this, it is
often restricted to the milder, adult form of the disease.
8. Osteomalacia is derived from Greek:
osteo bone
malacia softness
most commonly found in:
dark-skinned
diet-disbalanced subjects (mainly lactating females).
Age: adults
Site: WEIGHT-BEARING BONES such as vertebral bodies and femoral
neck
9. There are two main causes of osteomalacia:
1. insufficient calcium absorption from the intestine because of
lack of dietary calcium or a deficiency of, or resistance to, the
action of vitamin D; and
2. phosphate deficiency caused by increased renal losses.
10. Normal bone metabolism: CALCIUM
• CALCIUM 99% in bone.
• Main functions muscle /nerve function, clotting.
• Plasma calcium 50% free, 50% bound to albumin.
• Dietary needs:
• Kids: 600mg/day
• Adolescent 1300mg/day,
• Adult: 750mg/day
• Pregnancy: 1500mg/day,
• Breastfeeding: 2g/day,
• Fractures: 1500mg/day
• Absorbed in duodenum (active transport) and jejunum (diffusion),
98% reabsorbed in kidney prox. tubule, may be excreted in stool.
11. Normal bone metabolism: PHOSPHATE
PHOSPHATE 85% in bone.
Functions: metabolite and buffer in enzyme systems.
Plasma phosphate mainly unbound.
Daily requirement: 1-1.5g/day
12. Regulation of Calcium & Phosphate Metabolism:
1. Parathyroid Hormone (PTH)
2. Vitamin D3
3. Calcitonin
4. Other Hormones:
Estrogen: Prevents bone loss
Corticosteroids: Increases bone loss
Thyroid hormones: Leads to osteoporosis
Growth hormones: Cause positive calcium balance
Growth factors
17. A. Vitamin D Deficiency and Resistance
• Vitamin D deficiency is the most common cause of osteomalacia
• Deficiency of vitamin D may arise from insufficient sun exposure; malnutrition; or
malabsorption (due to pancreatic insufficiency, cholestatic liver disease, celiac
disease, inflammatory bowel disease, jejunoileal bypass, Billroth type II
gastrectomy); or orlistat use, which causes fat malabsorption.
18. • Anticonvulsants (eg, phenytoin, carbamazepine, valproate, phenobarbital) inhibit the
hepatic production of 25OHD and sometimes cause osteomalacia. Phenytoin can also
directly inhibit bone mineralization.
• Cholestyramine binds bile acids necessary for vitamin D absorption. Patients with
severe nephrotic syndrome lose large amounts of vitamin D–binding protein in the
urine.
• Vitamin D–dependent rickets type I is caused by a rare autosomal recessive disorder
with a defect in the renal enzyme 1-alpha-hydroxylase leading to defective synthesis
of 1,25(OH)2D. It presents in childhood with rickets and alopecia; osteomalacia
develops in adults with this condition unless treated with oral calcitriol in doses of
0.5–1 mcg daily.
19. • Vitamin D–dependent rickets type II (better known as hereditary 1,25[OH]2D-resistant
rickets) is caused by a genetic defect in the 1,25(OH)2D receptor. Patients have
hypocalcemia with childhood rickets and adult osteomalacia. Alopecia is common.
These patients respond variably to oral calcitriol in very large doses (2–6 mcg daily).
20. B. Deficient Calcium Intake
• A nutritional deficiency of calcium can occur in any severely malnourished patient.
• Some degree of calcium deficiency is common in older adults, since intestinal
calcium absorption declines with age. Ingestion of excessive wheat bran also causes
calcium malabsorption.
21. 1. Genetic disorders
• Fibroblast growth factor-23 (FGF23) is a phosphaturic factor (phosphatonin) that is
secreted by bone osteoblasts in response to elevated serum phosphate levels.
• Families with autosomal dominant hypophosphatemic rickets have a gain-of-function
mutation in
• the gene encoding FGF23 that makes it resistant to proteolytic cleavage, thereby
increasing serum FGF23 levels.
Osteomalacia develops in patients with hypophosphatemia due to lack of sufficient
phosphate to mineralize bone osteoid.
C. Phosphate Deficiency
22. • In X-linked hypophosphatemic rickets, there is a mutation in the gene encoding PHEX
endopeptidase, which fails to cleave FGF23, resulting in elevated serum FGF23 levels.
• An autosomal recessive form of hypophosphatemic rickets is caused by mutations in
DMP1, a transcription factor that regulates FGF23 production in bone.
• All three conditions have high serum FGF23 levels
23. 2. Tumor-induced osteomalacia
• A variety of mesenchymal tumors (87% benign) secrete fibroblast growth factor-23
(FGF23) and cause marked hypophosphatemia due to renal phosphate wasting.
• The condition is characterized by hypophosphatemia, excessive phosphaturia, reduced
or normal serum 1,25(OH)2D concentrations, and osteomalacia. Serum levels of
FGF23 are elevated.
24. 3. Other causes of hypophosphatemia
• Osteomalacia from hypophosphatemia can be caused by severe intestinal malabsorption
or poor nutrition. Severe hypophosphatemia can occur with refeeding after starvation (eg,
concentration camp victims, malnourished alcoholics).
• Other causes of hypophosphatemia include respiratory alkalosis,glucose infusions,
salicylate intoxication, mannitol, and bisphosphonate therapy.
• Additional causes include chelation of phosphate in the gut by aluminum hydroxide
antacids, calcium acetate (Phos-Lo), or sevelamer hydrochloride(Renagel). Excessive
renal phosphate losses are also seen in proximal renal tubular acidosis and Fanconi
syndrome
25. D. Aluminum Toxicity
Bone mineralization is inhibited by aluminum. Osteomalacia may occur in
patients receiving long-term renal hemodialysis with tap water dialysate or from
aluminum containing antacids used to reduce phosphate levels.
E. Hypophosphatasia
Hypophosphatasia refers to a severe deficiency of bone alkaline phosphatase. It is a rare
genetic cause of osteomalacia that is commonly misdiagnosed as osteoporosis.
29. SIGN AND SYMPTOMS
• osteomalacia is typically asymptomatic at first.
• Bone pain , backache
• Muscle weakness
• Vertebral collapse: kyphosis
• loss of height
• Deformities & stress fractures
30. • Osteomalacia in adults starts insidiously as aches and pains in
the lumbar region and thighs, spreading later to the arms and
ribs.
• Pain is non-radiating, symmetrical, and accompanied by tend
erness in the involved bones.
• Proximal muscles are weak, and there is difficulty in climbing
up stairs and getting up from a squatting position
SIGN AND SYMPTOMS
31. • Physical signs include deformities like lordosis.
• Pathologic fractures due to weight bearing may develop.
• Most of the time, the only alleged symptom is chronic and
bony ache which is only revealed by pressure or shocks.
SIGN AND SYMPTOMS
32. • Rickets
– Tetanus , convulsions, failure to thrive
– restlessness, muscular flaccidity
– Flattening of skull (craniotabes)
– Thickening of wrists from epiphyseal overgrowth, Stunted growth,
Rickety rosary, spinal curvature, Coxa vara, bowing,
– Fx of long bones
• Osteomalacia
– Aches and pains
– muscle weakness loss of height
– stress fx
SIGN AND SYMPTOMS
35. Work up for Osteomalacia
Ca , P , Alk ph
24 h urinary Ca
25 (OH) Vit-D
1 , 25 (OH) Vit-D
PTH
Bone Biopsy
Biochemistry
36. 1- ca P = Nl Alk ph
2- ca = Nl P Alk ph
3- ca P Alk ph
24 h Urinary ca < 100 mg / 24 h
24 h Urinary Hydroxyproline Excretion
Biochemistry
37. • Bone densitometry helps document the degree of osteopenia.
• Genetic testing can confirm the diagnosis of autosomal dominant hypophosphatemic
rickets (FGF23), X-linked hypophosphatemic rickets (PHEX), and autosomal recessive
hypophosphatemic rickets (DMP1).
• Patients with apparent tumor-induced osteomalacia with hypophosphatemia require
localization studies. Whole-body scanning with somatostatin analogs 68Ga-DOTATOC
PET/CT is the preferred imaging technique in this condition, detecting about 90% of
tumors in small series.
OTHER DIAGNOSTIC
METHODS
38. • To confirm the diagnosis of hypophosphatasia in patients with a low serum alkaline
phosphatase, a 24-hour urine should be assayed for phosphoethanolamine, a substrate
for tissue-nonspecific alkaline phosphatase whose excretion is always elevated in
patients with hypophosphatasia.The diagnosis is confirmed with genetic testing for
mutations in the ALPL gene.
39. COMPARISION OF
CONDITIONS
Condition Calcium Phosphate
Alkaline
Phosphate
Parathyroid
Hormone
Special
features
Osteopenia Unaffected Unaffected Normal Unaffected
Decrease d
bone mass
Osteoporosis Unaffected Unaffected Elevated Unaffected
Thick
dense
bones
Osteomalacia/Ri
ckets
Decreased Decreased
Elevated Elevated
Soft
bones
Osteitis
fibrosa
cystica
Elevated Decreased Elevated Elevated Brown
tumors
Paget’s
disease
unaffected decreased variable unaffected Abnormal
bone
structure
41. Loosers zones
– incomplete stress Fx with healing lacking
calcium, on compression side of long
bones.
Codfish vertebrae due to pressure of discs
Trefoil pelvis, due to indentation of
acetabulae stress fx
X-RAY
46. Prevention
• To obtain adequate sunshine vitamin D, the face, arms, hands, or back must have sun
exposure without sunscreen for 15 minutes at least twice weekly.
• The main natural food source of vitamin D is fish, particularly salmon, mackerel,cod
liver oil, and sardines or tuna canned in oil. Most commercial cow’s milk is fortified
with vitamin D at about 400 international units per quart; however, skim milk and other
dairy products contain much less vitamin D.
47. Depends on the cause
Nutritional Vitamin D deficiency
Dietary chelators of calcium
Phytates
Oxalates
Phosphorus deficiency (unusual)
Antacid abuse
TREATMENT
48. Depends on the cause
Gastro-intestinal absorption defects Po
st-gastrectomy Biliary
disease Enteric abs
orption defects
Short bowel syndrome
Rapid onset (gluten-sensitive enteropathy) Inflamm
atory bowel disease
Crohns
Celiac
TREATMENT
49. Depends on the cause
Renal tubular defects Vita
min D dependant
type I
type II
Treatment; High levels of vit D
Vitam
in D resistant (familial hypophosphatemic rickets)
Treatment; Phosphate 1-3 gm daily, Vit D3 high dose
Fanconi syndrome I, II, III R
enal tubular acidosis
TREATMENT
50. Depends on the cause
Renal Osteodystrophy – in chronic renal failure
Miscellaneous Hypophosphata
sia Anticonvulsant therapy
SURGERY
For deformities
TREATMENT
