by West Medical Ward King Edward Medical University , Lahore, Pakistan.

1. Parathyroid Disorders
Osteomalacia & Osteoporosis
Professor Tariq Waseem
Dr. Hina Latif

2. Botanical Garden Sydney

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.
What is the working diagnosis?
Which 3 bed side tests can be performed to confirm the
diagnosis?

4. • Tetany.
• Hypocalcemia.
• Trosseou’s sign
• Chvostek’s sign
• Brisk tendon Reflexes

5. Hypoparathyroidism

6. Parathormone(PTH)
PTH is an 84-amino acid
polypeptide derived from a
prohormone.
 It is the major hormone in Ca++
homeostasis.
NORMAL Ca LEVELS
9 to 10.5mg/dl
2.2 to 2.6 mmol/L

7. ACTIONS OF PTH
BONE
RESORPTION
PHOSPHATURIC
REABSORPTION OF
DIETARY Ca++
DISTAL RENAL TUBULAR
REABSORPTION OF Ca++

8. HYPOPARATHYROIDISM
• Iatrogenic
• Idiopathic (auto immune)
• Pseudohypoparathroidism (autosomal dominant)
• Pseudo pseudo hypoparathyroidism (normal Ca levels)

9. Albright’s Syndrome
(Pseudohypoparathyroidism)
Short 4th & 5th metacarpels
Low Serum Calcium, Normal PTH. PTH receptor deficiency

10. HYPOCALCEMIA
LARYNGOSPASM
CHVOSTEK SIGN
CONVULSIONS,
MENTAL
RETARDATION
PROLONGED
QT INTERVAL
HYPER
REFLEXIA
TROUSSEAU’S
SIGN
CATARACT
PAPPILOEDEMA
SKELETAL
DEFORMITIES

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.
Give a list of differential diagnosis?
What investigations will you request?

14. HYPERCALCEMIA

15. HYPERCALCEMIA

16. CAUSES OF HYPERCALCEMIA
• Primary or tertiary hyperparathyroidism
• Familial hypocalciuric hypercalcemia
• Malignancy
• Multiple myeloma
• Milk alkali syndrome
• Diuretics
• Paget’s disease
• Vitamin D intoxication
• Addison’s 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. INVESTIGATIONS….
• 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)

19. IMAGING

20. IMAGING…
SUB PERIOSTEAL RESORPTION BROWN TUMOR

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

22. Botanical Gardens Sydney

23. • A 40yrs old female, known epileptic, presented with
4months history of generalized muscular discomfort
particularly in her shoulders. The symptoms don’t 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

24. • Hb…10.9g/dl
• ESR…16mm/h
• Plasma glucose(post-parandial) ….7.6mmol/l
• HbA1C….5.6%
• S.calcium…7.4mg/dl
• Phosphate…2.5mg/dl
• Alkaline phosphatase…198 IU/L
• DIAGNOSIS??????
Subsequent investigations revealed:

25. • This Patient’s presentation with myalgia associated with
a combination of mild hypocalcemia, hypophosphatemia
and elevation of alkaline phosphatase is strongly
suggestive of OSTEOMALACIA.
OSTEOMALACIA

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 acidosis…RTA
Etiology

29. Causes of Osteomalacia:

30. • Bone pain
• Backache
• Muscle weakness…proximal myopathy
• Vertebral collapse…kyphosis, loss of height
• Deformities and stress fractures
• Difficulty in rising from a chair
• Difficulty in walking
• Waddling gait…sometimes
Sign & Symptoms:

31. Clinical presentation:

32. Laboratory tests:
• Increased serum alkaline phosphatase
• Plasma calcium…usually normal but decreased in
severe disease
• Low serum phosphate
• Serum 25OHD….low

33. X-RAYS:
• May show defective mineralization in pelvis, long bones
and ribs, with pseudofractures and LOOSER’S 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

35. Looser
Zones

36. Looser
Zones

40. • Illiac crest biopsy….necessary if biochemical tests are
equivocal
• Serum fibroblast FGF-23….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-hydroxylation…CKD,
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 phosphatase…to
screen for hypercalcemia
• Normalization of alkaline phosphatase…good measure
of healing
Monitoring:

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?

47. Challenges of Osteoporosis

48.  Being female
 Older age
 Family history of osteoporosis or broken bones
 Being small and thin
 History of broken bones
 Low sex hormones
• Low estrogen levels in women, including
menopause
• Missing periods (amenorrhea)
• Low levels of testosterone and estrogen in men

49.  Diet
• Low calcium intake
• Low vitamin D intake
• Excessive intake of protein,
sodium and caffeine
 Inactive lifestyle
 Smoking , Alcohol abuse
 Certain medications
• steroid , anticonvulsants etc
 Certain diseases
• anorexia nervosa, rheumatoid
arthritis, gastrointestinal
diseases and others

50. National Osteoporosis Foundation:
 a disease characterized by low
bone mass an micro-architectural
deterioration of bone tissue,
leading to bone fragility and an
increased susceptibility to
fractures.”
World Health Organization (1994) :
 bone mineral density T-score
greater than –2.5 standard
deviations from the mean peak
adult bone mass (ie. a woman in
her 30’s).”

51.  Primary osteoporosis
• Juvenile osteoporosis.
• Idiopathic osteoporosis
• Postmenopausal
osteoporosis
• Age-related, or senile,
osteoporosis
• Secondary osteoporosis
• Congenital
• Diet
• Drugs
• Endocrine disorder
• Other Systemic
Disorder

52. Losing bone with years

53. Worldwide, over age of 50
 1 in 3 women
 1 in 8 men have osteoporosis.
 Caucacian and asian races..at risk
 80 % of those suffering from osteoporosis are women.
 Affects 75 million persons in the US, Europe and Japan.
 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 “silent disease”
• Often called the
“silent disease”
• 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.  People may not know that they
have osteoporosis until they break
a bone.
 Vertebral (spinal) fractures may
initially be felt or seen in the form
of
 Persistent, unexplained back
pain
 Loss of height
 Spinal deformities such as
kyphosis or stooped posture.

57.  Plain radiographs…may reveal asymptomatic
vertebral deformities
 Dual-energy X-ray Absorptiometry (DXA) Scan
• “Gold-standard” for BMD measurement.
• Measures “central” or “axial” 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 calcenum…screening
procedure before DXA
• Quantative CT scanning…allows true volumetric
assessment, and distinction b/w trabecular and cortical
bone
Bone density:

59.  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
 Increased morbidity
 Increased mortality
 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 management…of vertebral fractures, bed
rest for 1-2 weeks, analgesics
• Calcium and vitamin D
• Exercise
• Smoking cessation
• Reduce falls…physiotherapy & home safety
• Pharmacological intervention…anti-resorptive drugs,
bisphosphonates, SERM, HRT, calcitriol, calcitonin etc…
Treatment and prevention:

65.  Prevent further bone loss
 Increase or at least stabilize bone density
 Prevent further fractures
 Relieve deformity (e.g., kyphoplasty)
 Relieve pain
 Increase level of physical functioning
 Increase quality of life

66.  Supplements which maintain bone mass Calcium (
700-1000mg/day), Vitamin D( 400-800 IU/day)
 Anti-resorptive agents
 which inhibit bone resorption Bisphosphonates
 Anabolic agents,
 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 2–4 mg I/V over
15–30 minutes.
Pamidronate: an older parenteral bisphosphonate given in
doses of 30–60 mg by slow i/V infusion in every 3–6 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 μg 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. Measures…to 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 30–40% 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:

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?

76. DEXA Scan

77. DEXA Scan

78. DEXA Scan

79. Diagnosis
Osteogenesis Imperfecta

80. “Three Sisters”
Blue Mountains Australia