metabolic bone diseases

1. METABOLIC BONE
DISEASES

2. • Calcium and Phosphate ion regulation
• Vitamin D metabolism and absorption
• Effects of active vitamin D
• PTH (primary, secondary, tertiary)
• Paget’s disease (classification, clinical
manifestations, treatment)
• Rickets (classification, clinical
manifestations, treatment)

3. Bone remodeling (bone metabolism)
• A lifelong process where
mature bone tissue is removed from the
skeleton (a process called
bone resorption) and new bone tissue
is formed (a process called ossification
or new bone formation).

4. Bone remodeling occurs in
four steps:
1. Activation,
2. Osteoclast resorption,
3. Surface preparation,
4. Building new bone
tissue.

5. Metabolic Bone Disorders
• Metabolic bone diseases are disorders of bone
strength, usually caused by abnormalities of
minerals (such as calcium or phosphorus),
vitamin D, bone mass or bone structure.
• At times occur because bone formation and
remodelling is not prioritized if the materials are
required more urgently somewhere else (e.g.
muscle contraction and coagulation).

6. Calcium and Phosphate
regulation
• Following two are responsible for the regulation
and supply of calcium and phosphate for the bone
formation:
1. Active Vitamin D (1,25, Dihydrocholecalciferol)
2. Parathyroid Hormone

8. Vitamin D metabolism

10. 1,25-dihydroxycholecalciferol
• Increases absorption of calcium from intestines.
• Increase absorption of phosphate from the intestines.
• Decreases calcium excretion in the kidney.
• PTH production supression.
• Regulates Osteoblast function.
• Facilitate PTH induced Osteoclast function.
OVER ALL:
• Increases calcium in blood.
• Increases PO4 in blood.
• Aids bone formation.

11. Vitamin D sources

12. Parathyroid Hormone
• Increases renal reabsorption of calcium.
• Releases calcium from skeletal stores.
• Increases the bone resorption of calcium.
• Decreases renal reabsorption of phosphate.
• Increases the bone resorption of phosphate.
OVER ALL:
• Increases serum calcium levels.
• Bone resroption (chronic continuous excess).

14. Hyperparathyroidism
• Hyperparathyroidism is overactivity of the parathyroid glands resulting
in excess production of parathyroid hormone (PTH). The parathyroid
hormone regulates calcium and phosphate levels and helps to maintain
these levels.

15. Primary hyperparathyroidism
• Primary hyperparathyroidism causes hypercalcemia (elevated
blood calcium levels) through the excessive secretion
of parathyroid hormone (PTH), usually by an adenoma (benign
tumors) of the parathyroid glands. It is the commonest cause of
elevated calcium levels.

16. • “Stones" refers to kidney stones, nephrocalcinosis, and diabetes
insipidus (polyuria and polydipsia). These can ultimately lead
to renal failure.
• "Bones" The classic bone disease in hyperparathyroidism
is osteitis fibrosa cystica, which results in pain and sometimes
pathological fractures. Other bone diseases associated with
hyperparathyroidism are osteoporosis, osteomalacia,
and arthritis.
• "Abdominal groans”
of constipation, indigestion, nausea and vomiting.
Hypercalcemia can lead to peptic ulcers and acute pancreatitis.
The peptic ulcers can be an effect of increased gastric
acid secretion by hypercalcemia.

17. • "Psychiatric moans" lethargy, fatigue, depression, memory loss,
psychosis, ataxia, delirium, and coma.
• "Thrones" refers to polyuria and constipation
• Left ventricular hypertrophy.
• Other signs include proximal muscle weakness, itching, and band
keratopathy of the eyes.

19. • Labs: Serum calcium levels are elevated, and the parathyroid
hormone level is abnormally high compared with an expected
low level in response to the high calcium. A relatively elevated
parathyroid hormone has been estimated to have a sensitivity of
60%-80% and a specificity of approximately 90% for primary
hyperparathyroidism. Serum phosphorus will decrease.
• Imaging: radio labeled technitium 99m remains in adenomas.
• Treatment: usually surgical removal of the gland(s) containing
adenomas, but medication may also be required.

20. The brown tumor is a
bone lesion that arises in
settings of
excess osteoclast activity,
such
as hyperparathyroidism.

21. Secondary hyperparathyroidism
• Secondary hyperparathyroidism refers to the excessive
secretion of parathyroid hormone (PTH) by
the parathyroid glands in response
to hypocalcemia (low blood calcium levels) and associated
hypertrophy of the glands. This disorder is especially seen
in patients with chronic renal failure.
• Clinical features: Bone and joint pain are common, as
are limb deformities. The elevated PTH has also
pleiotropic effects on blood, immune system and
neurological system.

22. • Labs: The PTH is elevated due to decreased levels of
calcium or 1,25-dihydroxy-vitamin D3. It is usually seen in
cases of chronic renal disease or defective calcium
receptors on the surface of parathyroid glands. Serum
phosphorus will increase.
• Treatment: If the underlying cause of the
hypocalcemia can be addressed, the
hyperparathyroidism will resolve.
• In patients with chronic renal failure, treatment
consists of dietary restriction of phosphorus,
supplements with an active form of vitamin D such
as calcitriol, Hectorol, Zemplar(paricalcitol), etc.
and phosphate binders which can be divided into
calcium-based and non-calcium based.

23. Subperiosteal resorption
Thirty year-old patient with
chronic renal failure and
elevated parathyroid
hormone.
Subperiosteal resorption is
most evident on the radial
sides of proximal and
middle phalanges.
Note the shaggy outer
cortical surface in the mid-to-
distal shaft of the middle
finger proximal phalanx.

24. Tertiary hyperparathyroidisim
• Tertiary hyperparathyroidism is a state of excessive secretion of parathyroid
hormone (PTH) after a long period of secondary hyperparathyroidism and
resulting in hypercalcemia. It reflects development of autonomous (unregulated)
parathyroid function following a period of persistent parathyroid stimulation.
• Serum calcium increases. PTH levels are increased. Serum phosphorus remains
increased.
• The basis of treatment is still prevention in chronic renal failure, starting
medication and dietary restrictions long before dialysis treatment is
initiated. Cinacalcet has greatly reduced the number of patients who ultimately
require surgery for secondary hyperparathyroidism; however, 5% of patients do
not respond to medical therapy.
• When secondary hyperparathyroidism is corrected and the parathyroid
glands remain hyperfunctioning, it becomes tertiary hyperparathyroidism. The
treatment of choice is surgical removal of three and one half parathyroid glands.

26. Paget’s disease of the bone
• Paget Disease of Bone, or osteitis deformans, is a
condition of older individuals characterized by progressive
skeletal deformation due to problems in bone resorption
and remodeling. Likely due to a viral infection, it stimulates
an increase in osteoclast activity. This leads to increased
bone resorption coupled with abnormal and excessive
bone remodeling.
• It is relatively common and can affect up to 4% of
individuals over 40 and up to 11% over the age of
80 1. There may a slight male predilection.

27. Clinical features
• Paget Disease is often asymptomatic and may take
months to years to diagnose. Skeletal bone deformity and
enlargement may be the first presentation.
• localised pain and tenderness
• increased focal temperature due to hyperaemia (due
to hypervascularity)
• increased bone size: historically changing hat size
was a give-away
• bowing deformities
• kyphosis of the spine
• decreased range of motion

28. Stages
There are three stages classically described (but is part of
continuous spectrum)
• lytic (incipient active): predominated by osteoclastic activity
• mixed (active): osteoblastic as well as osteoclastic activity
• sclerotic/blastic (late inactive)
Markers
• serum alkaline phopatase (ALP) elevated
• urine hydroxyproline increase
Imaging
• Xray (skull, pelvis, humerus, femur)
• CT scan (Vertebrae, Skull)
• MRI
• Bone Scan

29. Complications
• osseous weakening resulting in deformity and fractures
• arthritis
• neural compression
– deafness is the most common complication
– cranial nerve paresis may occur
– basilar invagination may occur in advanced cases
with hydrocephalus orbrainstem compression
• secondary development of tumours (e.g. osteosarcoma: ≈1%
of cases), which is often highly resistant to treatment
• high output congestive cardiac failure
• hyperparathyroidism (~10%)
Treatment
• Calcitonin – Inhibits osteoclast formation.
• Bisphosphonates – Induces apoptosis of osteoclasts.

30. Sites of involvement
• Usually polyostotic and asymmetric
– Pelvis (75%) most common, followed by:
• Lumbar spine
• Thoracic spine
• Proximal femur
• Calvarium
• Scapula
• Distal femur
• Proximal tibia
• Proximal humerus

31. This 92 year-old male patient
presented for assessment of
acute hemiparesis.
An incidental finding was
marked thickening of the
calvarium.
The diploic space is widened
and there are ill-defined sclerotic
and lucent areas throughout.
The cortex is thickened and
irregular.
The findings probably
correspond to the “cotton wool
spots” seen on plain films in the
later stages of Paget’s disease.

32. Paget's disease of the skull.
Demonstrate the Tam O'Shanter sign

33. Bone scan
demonstrates
intense uptake
involving several
lower thoracic
vertebrae, L3, right
hemipelvis, sacrum,
left proximal femur
and right knee.
There is expansion
and bowing of the
involved femur.

34. There is osseous
expansion,
coarsened
trabeculae,
thickened
cortex, and
increased density of
the right 5th rib.

35. Paget disease of the
distal femur in an 80
year old male
characterized by
cortical thickening
and coarsened bony
trabeculae.
There is mild loss of
medial tibiofemoral
compartment joint
space without
secondary
degenerative
features.

36. Lateral radiograph of the
tibia in a patient with
Paget sarcoma reveals a
destructive bone-forming
mass in the proximal tibia
(osteosarcoma).

37. Blade of grass
sign (candle flame
appearance) in lytic
phase Paget's
disease of bone.

38. Rickets
• Rickets is the softening and weakening of bones in
children, usually because of an extreme and prolonged
vitamin D deficiency.
• Vitamin D promotes the absorption of calcium and
phosphorus from the gastrointestinal tract. A deficiency of
vitamin D makes it difficult to maintain proper calcium and
phosphorus levels in bones, which can cause rickets.
• If a vitamin D or calcium deficiency causes rickets, adding
vitamin D or calcium to the diet generally corrects any
resulting bone problems for your child. Rickets due to a
genetic condition may require additional medications or
other treatment. Some skeletal deformities caused by
rickets may need corrective surgery.

40. Signs and symptoms of rickets may include:
• Bone pain or tenderness
– Arms, Legs, Pelvis, Spine
• Dental deformities
• Impaired growth
• Increased bone fractures
• Muscle cramps
• Short stature (adults less than 5 feet tall)
• Skeletal deformities
– Asymmetrical or odd-shaped skull
– Bowlegs
– Bumps in the ribcage (rachitic rosary)
– Breastbone pushed forward (pigeon chest)
– Pelvic deformities
– Spine deformities (spine curves abnormally,
including scoliosis or kyphosis)

41. Risk factors
• Age Children 3 to 36 months old are most at risk of rickets
because their skeletons are growing so rapidly.
• Dark skin Dark skin doesn't react as strongly to sunshine as
does lighter colored skin, so it produces less vitamin D.
• Northern latitudes Children who live in geographical
locations where there is less sunshine are at higher risk of
rickets.
• Premature birth Babies born before their due dates are more
likely to develop rickets.
• Anti-seizure medications. Certain types of anti-seizure
medications appear to interfere with the body's ability to use
vitamin D.
• Exclusive breast-feeding Breast milk doesn't contain
enough vitamin D to prevent rickets. Babies who are
exclusively breast-fed should receive vitamin D drops.

43. Angular deformities

44. Cupping of radius
and ulna

45. Complications
• If left untreated, rickets may lead to:
• Failure to grow
• Abnormally curved spine
• Skeletal deformities
• Dental defects
• Seizures
Labs
• Serum calcium may show low levels of calcium,
serum phosphorus may be low, and serum alkaline
phosphatase may be high from bones or changes in
the shape or structure of the bones. This can show
enlarged limbs and joints.
• Bone biopsy is rarely performed but will confirm rickets.

46. Treatment
• Replacing calcium, phosphorus, or vitamin D that is
lacking will eliminate most symptoms of rickets.
Dietary sources of vitamin D include fish, liver, and
processed milk.
• Exposure to moderate amounts of sunlight is
encouraged. If rickets is caused by a metabolic
problem, a prescription for vitamin D supplements
may be needed.
• 400 international units (IU) of vitamin D a day for
infants and children.
• Positioning or bracing may be used to reduce or
prevent deformities. Some skeletal deformities may
require corrective surgery.

47. Blount's disease is a growth disorder of the tibia (shin bone) that causes the
lower leg to angle inward, resembling a bowleg.
It is also known as "tibia vara".[1]
Photos of a child with Blount's
Disease in a brace.

48. • In surgical correction of Blount’s disease, the pediatric orthopedist
performs an osteotomy, cutting the tibia and fibula as close to the
growth plate as possible and realigning the bones. Following the
procedure, the surgeon places a fixator on the leg to maintain
proper alignment during healing.

49. THANK YOU