3. CASE SCENARIO: 1
A 20yr old girl presented in E.R with h/o of convulsions for
the last 3 hrs. Examining her the house officer noticed a
stridor and observed spasm of her hands while he was
recording her blood pressure.
ďWhat is the working diagnosis?
ďWhich 3 bed side tests can be performed to confirm the
diagnosis?
6. Parathormone(PTH)
ď§PTH is an 84-amino acid
polypeptide derived from a
prohormone.
ď§ It is the major hormone in Ca++
homeostasis.
NORMAL Ca LEVELS
9 to 10.5mg/dl
2.2 to 2.6 mmol/L
11. DIFFERNTIAL DIAGNOSIS
Ca IONIZED Ca PO4 PTH
HYPOALBUMINEMIA L N N N
ALKALOSIS N L N N/H
VIT D DEFICIENCY L L L H
HYPO-
PARATHYROIDISM
L L H L
PSEUDO HYPO
PARATHYROIDISM
L L H H
ACUTE PANCREATITIS L L L/N H
RENAL FAILURE L L H H
12. MANAGEMENT
⢠Treat alkalosis (Rebreathing exhaled air through a bag)
⢠Inj calcium gluconate 10mg in 10ml over 10 mins.
⢠Magnesium sulphate
⢠1 alpha hydroxy cholecalciferol
13. CASE SCENARIO: 2
A 55 yr old male presented in E.R holding his right
flank. He complains of a severe right sided lumbar
pain , excessive vomiting & constipation for 2days.
He has a dry tongue with vitals of B.P 150/110mmHg,
pulse 110/min . On USG KUB radio opaque stones
are seen in the right kidney.
ďGive a list of differential diagnosis?
ďWhat investigations will you request?
16. CAUSES OF HYPERCALCEMIA
⢠Primary or tertiary hyperparathyroidism
⢠Familial hypocalciuric hypercalcemia
⢠Malignancy
⢠Multiple myeloma
⢠Milk alkali syndrome
⢠Diuretics
⢠Pagetâs disease
⢠Vitamin D intoxication
⢠Addisonâs disease
NORMAL OR ELEVATED PTH
LOW PTH
17. TYPES OF HYPERPARATHYROIDISM
TYPES Ca PTH PO4 ALP URINE
Ca/PO4
PRIMARY H N/H L H H
SECONDARY L H H H L
TERTIARY H N/ H H H
MALIGNANCY H L/N L H
18. INVESTIGATIONSâŚ.
⢠Screen for malignancy
⢠Chest X ray, bone scan, X ray hands
⢠CT neck
⢠Rule out Multiple Myeloma.
Serum protein electrophoresis, benze jones
proteins,immunoglobulins
⢠Sarcoidosis ( ACE levels)
21. MEDICAL MANAGEMENT
REHYDRATE
WITH 4-6 LITRES OF SALINE
BISPHOSPHONATES
PRAMIDRONATE 90mg I.V over 4 hrs till cause is
removed.
FORCED DIURESIS (FUROSEMIDE)
GLUCOCORTICOIDS
CALCITONIN
DIALYSIS
23. ⢠A 40yrs old female, known epileptic, presented with
4months history of generalized muscular discomfort
particularly in her shoulders. The symptoms donât worse
in the morning with non-specific relieving factors. Her
weight is stable.
⢠Examination reveals only mild proximal weakness in
both arms and legs with preserved reflexes
Case scenario: 3
25. ⢠This Patientâs presentation with myalgia associated with
a combination of mild hypocalcemia, hypophosphatemia
and elevation of alkaline phosphatase is strongly
suggestive of OSTEOMALACIA.
OSTEOMALACIA
26.
27. ⢠Rickets and osteomalacia are conditions
characterized by pathological defects in bone matrix
mineralization. Rickets refers specifically to
osteomalacia, where the defect occurs in growing bone.
⢠The aetiological factors are diverse, but the end
result is an increased quantity of unmineralized bone
matrix (osteoid).
RICKETS AND OSTEOMALACIA
28. The conditions may arise in three distinct
situations:
⢠Deficiency or abnormal metabolism of vitamin D
⢠Phosphate depletion
⢠Chronic metabolic acidosisâŚRTA
Etiology
30. ⢠Bone pain
⢠Backache
⢠Muscle weaknessâŚproximal myopathy
⢠Vertebral collapseâŚkyphosis, loss of height
⢠Deformities and stress fractures
⢠Difficulty in rising from a chair
⢠Difficulty in walking
⢠Waddling gaitâŚsometimes
Sign & Symptoms:
32. Laboratory tests:
⢠Increased serum alkaline phosphatase
⢠Plasma calciumâŚusually normal but decreased in
severe disease
⢠Low serum phosphate
⢠Serum 25OHDâŚ.low
33. X-RAYS:
⢠May show defective mineralization in pelvis, long bones
and ribs, with pseudofractures and LOOSERâS zones
⢠Linear areas of low density
surrounded by sclerotic
bone.
Imaging
34. X-ray findings:
Loosers zones - incomplete
stress # 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 #s
40. ⢠Illiac crest biopsyâŚ.necessary if biochemical tests are
equivocal
⢠Serum fibroblast FGF-23âŚ.sometimes elevated in tumor
associated osteomalacia.
Further Diagnostic tests:
41. Depends on the underlying cause;
⢠Vitamin D supplementation
⢠Phosphate supplements if required
⢠Calcium supplements for isolated calcium deficiency
⢠Bicarbonate if chronic acidosis
Treatment:
42. ⢠Vitamin D : 400-800IU/day for nutritional deficiency.
⢠Higher doses or parenteral administration in pts with
gastrectomy, liver disease, on epileptic medications
⢠Calcitriol or alfacalcidol
For defective 1a-hydroxylationâŚCKD,
Vit. D dependency,
Hypophosphatemic rickets with osteomalacia
Treatment:
43. ⢠Correction of the fracture
⢠Deformities stabilization
⢠DIET THERAPY:
⢠Milk, yogurt, cheese
⢠Dark green leafy vegetables, okra, broccoli
⢠Fish and seafood
⢠Almonds
Treatment:
44. ⢠Monitoring of serum calcium, alkaline phosphataseâŚto
screen for hypercalcemia
⢠Normalization of alkaline phosphataseâŚgood measure
of healing
Monitoring:
45.
46. Case Scenario: 4
⢠A 65 year old lady on long term steroids for bronchial
asthma is brought to ER after she fell in wash room and
could not stand up due to severe pain in and around her
left hip and lower back.
⢠X-rays showed fracture on left femoral neck and
markedly reduced density of Lumber vertebrae.
⢠What bone disease she has?
⢠What are risk factors for this disease?
48. ď§ Being female
ď§ Older age
ď§ Family history of osteoporosis or broken bones
ď§ Being small and thin
ď§ History of broken bones
ď§ Low sex hormones
⢠Low estrogen levels in women, including
menopause
⢠Missing periods (amenorrhea)
⢠Low levels of testosterone and estrogen in men
49. ď§ Diet
⢠Low calcium intake
⢠Low vitamin D intake
⢠Excessive intake of protein,
sodium and caffeine
ď§ Inactive lifestyle
ď§ Smoking , Alcohol abuse
ď§ Certain medications
⢠steroid , anticonvulsants etc
ď§ Certain diseases
⢠anorexia nervosa, rheumatoid
arthritis, gastrointestinal
diseases and others
50. National Osteoporosis Foundation:
ď§ a disease characterized by low
bone mass an micro-architectural
deterioration of bone tissue,
leading to bone fragility and an
increased susceptibility to
fractures.â
World Health Organization (1994) :
ď§ bone mineral density T-score
greater than â2.5 standard
deviations from the mean peak
adult bone mass (ie. a woman in
her 30âs).â
53. Worldwide, over age of 50
ď§ 1 in 3 women
ď§ 1 in 8 men have osteoporosis.
ď§ Caucacian and asian races..at risk
ď§ 80 % of those suffering from osteoporosis are women.
ď§ Affects 75 million persons in the US, Europe and Japan.
ď§ Over 50% of women aged 50 years or older and 20% of men
will suffer an osteoporosis-related fracture within their
remaining lifetime
54. SECONDARY CAUSES OF OSTEOPOROSIS
Endorine disecase
1. Hypogonadism*
2.Hyperparathyroidism
3 .Hyperthyroidism
4.Cushing's syndrome
5. Type 1 diabetes mellitus
Inflammatory disease
1. Inflammatory bowel disease .
2.Ankylosing spondylitis
3.Rheumatoid arthritis .
Gastrointestinal disease
1. Malabsorption
2.Chronic liver disease
* Hypogonadism plays an important role in
osteoporosis associated with these
conditions.
Drugs
1.Corticosteroids
2.Gonadotrophin-releasing hormone (GnRH)
agonists*
3.Aromatase inhibitors
4.Thyroxine over-replacement
5.Sedatives 6. Rosiglitazone
7.Anticonvulsants
8. Alcohol excess 9.Heparin .10. Cyclosporine
Miscellaneous
1.Myeloma
2.Homocystinuria
3.Anorexia nervosa*
4.Highly trained athletes*
5.Gaucher's disease
6.Systemic mastocytosis
7.Immobilisation
8.Poor diet/low body weight .
9. Osteogenesis imperfecta
55. The âsilent diseaseâ
⢠Often called the
âsilent diseaseâ
⢠Bone loss occurs
without symptoms
⢠First sign may be a
fracture due to
weakened bones
⢠A sudden strain or
bump can break a
bone
56. ď§ People may not know that they
have osteoporosis until they break
a bone.
ď§ Vertebral (spinal) fractures may
initially be felt or seen in the form
of
ď§ Persistent, unexplained back
pain
ď§ Loss of height
ď§ Spinal deformities such as
kyphosis or stooped posture.
57. ď§ Plain radiographsâŚmay reveal asymptomatic
vertebral deformities
ď§ Dual-energy X-ray Absorptiometry (DXA) Scan
⢠âGold-standardâ for BMD measurement.
⢠Measures âcentralâ or âaxialâ skeletal sites: spine
and hip( proximal femur)
⢠May measure other sites: total body and forearm.
⢠Precise, accurate, uses low dose of radiations
58. ⢠Quantative ultrasound of the calcenumâŚscreening
procedure before DXA
⢠Quantative CT scanningâŚallows true volumetric
assessment, and distinction b/w trabecular and cortical
bone
Bone density:
59. ď§ Dual-energy X-ray Absorptiometry (DXA) Scan
Classification T-score
Normal -1 or greater
Osteopenia Between -1 and -2.5
Osteoporosis -2.5 or less
Severe Osteoporosis
-2.5 or less
and fragility fracture
60. Investigations (continued)
INDICATIONS FOR BONE DENSITOMETRY :
Low trauma fracture (fall from standing height or less)
Clinical features of osteoporosis (height loss, kyphosis)
Osteopenia on plain X-ray
Corticosteroid therapy (> 7.5 mg prednisolone daily for >
3 months)
Family history of osteoporotic fracture
Low body weight (body mass index < 19)
Early menopause (< 45 years)
Diseases associated with osteoporosis
Assessing response of osteoporosis to treatment
61. FRACTURE ,
The most serious complication of
Osteoporosis that leads to
ď§ Increased morbidity
ď§ Increased mortality
ď§ Decreased quality of life
62. Complications:
Wrist fracture
men 1 in 40 (2.5%)
women 1 in 6
(16%)
Spinal fracture
men 1 in 20 (5%)
women 1 in 6 (16%)
Hip fracture
men 1 in 17 (6%)
women 1 in 6 (17.5%)
63. Decreased fracture risk
Life style modification Therapeutic Intervention
⢠Minimizing risk factors Slowing/stopping
bone loss
⢠Minimizing factors that
Contribute to fall
Maintaining or increasing
bone density and
strength
Maintaining or improving
bone microarchitecture
64. ⢠Symptomatic managementâŚof vertebral fractures, bed
rest for 1-2 weeks, analgesics
⢠Calcium and vitamin D
⢠Exercise
⢠Smoking cessation
⢠Reduce fallsâŚphysiotherapy & home safety
⢠Pharmacological interventionâŚanti-resorptive drugs,
bisphosphonates, SERM, HRT, calcitriol, calcitonin etcâŚ
Treatment and prevention:
65. ď§ Prevent further bone loss
ď§ Increase or at least stabilize bone density
ď§ Prevent further fractures
ď§ Relieve deformity (e.g., kyphoplasty)
ď§ Relieve pain
ď§ Increase level of physical functioning
ď§ Increase quality of life
66. ď§ Supplements which maintain bone mass Calcium (
700-1000mg/day), Vitamin D( 400-800 IU/day)
ď§ Anti-resorptive agents
ď§ which inhibit bone resorption Bisphosphonates
ď§ Anabolic agents,
ď§ which stimulate bone formation and, in turn, increase
bone mass.
67. 1.Bisphosphonates: synthetic analogues of bone
pyrophosphate, adher to hydroxyapatite and inhibit
osteoclasts.
Alendronate: 70 mg orally once weekly (tablet or
solution)
Risedronate: 35 mg orally once weekly
Ibandronate sodium:is taken once monthly in a
dose of 150 mg orally .
Pharmacologic therapy:
68. Management (continued)
Zoledronic acid: every 12 months in doses of 2â4 mg I/V over
15â30 minutes.
Pamidronate: an older parenteral bisphosphonate given in
doses of 30â60 mg by slow i/V infusion in every 3â6 months
2. Hormone replacement therapy (HRT) : For oral estrogens,
0.3 mg/d for esterified estrogens, 0.625 mg/d for conjugated
equine estrogens, and 5 g/d for ethinyl estradiol.
For transdermal estrogen, the commonly used dose supplies
50 g estradiol per day.
69. 3. Selective estrogen receptor modulators(SERMs):
Raloxifene, 60 mg/d orally,Tamoxifen.
4. Calcitriol (1,25-(OH)2D3): may reduce vertebral
fracture rate.
5. Calcitonin: binds to receptors on
osteoclasts,dose is one puff (0.09 mL, 200IU)
once daily, alternating nostrils.
Management (continued)
70. Management (continued)
6. Parathyroid hormone (PTH): stimulate bone formation.
Teriparatide daily s/c injection of 20 Îźg over a 12-18-
month period. Increases BMD by 10% or more.
7. Strontium ranelate: weak anti-resorptive activity, 2 g
daily
8. Denosumab: monoclonal antibody that inhibits
osteoclast activation,60 mg s/c every 6 months.
71. Nonpharmacologic Approaches:
a.Kyphoplasty and vertebroplasty
b. MeasuresâŚto avoid falls at home adequate
lighting, handrails on stairs, handholds in
bathrooms. Patients who have weakness or
balance problems must use a cane or a walker.
Management (continued)
72. Treatment Monitoring
⢠Response to treatment can be monitored either by
repeated BMD measurement or by measuring
biochemical markers of bone turnover.
⢠Changes must exceed ~4% in the spine and 6% in the
hip to be considered significant in any individual.
⢠BMD should be repeated at intervals >2 years.
73. ⢠If bone turnover markers are used, a change in
bone turnover markers must be 30â40% lower
than the baseline to be significant.
⢠If neither BMD nor biochemical markers are
available, treatment response can be assessed
by monitoring changes in height and the
occurrence of clinical fractures.
Treatment monitoring:
74.
75. Case Scenario: 5
⢠A 14 year old girl consults for fever which she has for 3
weeks. She has a history of recurrent fractures of long
bones of forearm and legs since the age of Six on minor
trauma. Latest fracture involving left mid femur was fixed
through intramedullary rod insertion 6 months ago. Her
IM rod was removed 4 weeks ago.
Labs. Review: Normal calcium, phosphorus, vitamin D,
parathormone.
What bone disease she possibly has?
What diagnostic test will help to reach a diagnosis?