Chap.75-Metabolic Bone Disease

Question 0

OFC (osteitis fibrosa cystica) results from chronically elevated parathyroid hormone (PTH) concentrations, in turn, may result from …..
primary and tertiary hyperparathyroidism are characterized by ______ , whereas those with secondary hyperparathyroidism is characterized by ______.
*answer assoc. w/ calcium levels

Answer 0

primary & tertiary = hypercalcemia

secondary = eucalcemic or hypocalcemia

Question 1

\_\_\_\_\_ = caused by parathyroid adenoma, carcinoma, or hyperplasia
\_\_\_\_ = caused by malabsorption, vitamin D deficiency, or chronic renal failure
\_\_\_\_ = renal failure

Answer 1

1. primary hyperparathyroidism
2. secondary hyperparathyroidism
3. tertiary hyperparathyroidism

Question 2

What is another name for hyperparathyroid bone disease?

Answer 2

Osteitis Fibrosa Cystica

Question 3

What do patients with osteitis fibrosa cyctica complain of?

Answer 3

bone pain or diffuse aches and pains

Question 4

What is the skeletal disease (hyperparathyroid disease) osteitis fibrosa cystica characterized by?

Answer 4

high turnover
- meaning coupled increases in BOTH osteoclastic bone resorption and osteoblastic synthesis of osteoid and accelerated rates of bone mineralization.

Question 5

Osteitis fibrosa cystica:
What markers are used for bone formation?
What markers are used for bone resorption?
How can you check these changes?

Answer 5

formation = Alkaline phosphatase & Osteocalcin
resorption = N-telopeptide, hydroxyproline, and deoxypyridinolines
**THese changes are reflected on undecalcified bone biopsy, which reveals increases in the number of osteoclasts and osteoblasts, increased quantities of unmineralized (determined using tetracycline labeling), microcysts in cortex and trabeculae (the *cystica of OFC), and increased numbers of fibroblasts and marrow stroma (the *fibrosa of OFC)

Question 6

Bone density may be normal, assessed using DXA, or it may be low. The pathognomonic radiologic signs of severe hyperparathyroidism are a 1. _______ appearance of the calvarium, resorption of the tufts of the 2.__________, subperiosteal resorption of the _3.________, and _4.______ of the pelvis and long bones.

Answer 6

1. salt and pepper appearance of the calvarium
2. resorption of the tufts of the terminal phalanges and distal clavicles
3. subperiosteal resorption of the radial aspects of the second phalanges
4. Brown Tumors (actually collections of osteoclasts that produce gross lytic leasions) of the pelvis and long bones

Question 7

What does a parathyroidectomy cause in hyperparathyroid bone disease?

Answer 7

• parathyroidectomy - all the radiologic signs disappear

- boss mass - assessed by DXA - typically increases rapidly and markedly after parathyroidectomy

Question 8

What is the treatment of hyperparathyroid bone disease?

Answer 8

involves remediation of the chronically elevated PTH concentrations, either through parathyroidectomy in primary or tertiary hyperparathyroidism or through correction of the underlying cause of secondary hyperparathyroidism

Question 9

Recently, reduction in serum calcium using the parathyroid calcium receptor mimic drug ______, has been used.

Answer 9

Cincacalet

• indicated in patients with chronic renal failure with secondary hyperparathyroidism and in patients with parathyroid carcinoma who have failed surgical resection.
• *** although cincacalcet is effective in lowering the serum calcium in primary hyperparathyroidism, evidence of its efficacy in correcting skeletal abnormalities is lacking, and it is not approved for indication.

Question 10

Moderate to severe _____ may postoperatively accompany parathyroidectomy. This condition is referred to as ______ and results from what?

Answer 10

hypocalcemia; Hungry Bone Syndrome

• results from the sudden removal of the stimulus to osteoclastic activity by removing excess PTH in the setting of increased osteoblastic activity with unmineralized, but continuously mineralizing, osteoid
• the syndrome abates when the osteoid mineralizes

Question 11

Hyperparathyroid bone disease may be ____, as in a patient with severe primary hyperparathyroidism caused by a parathyroid adenoma, or it may be _____, occuring as a component of the bone disease in vitamin D-deficient osteomalacia, in immosuppressant-induced transplant bone disease, or in renal osteodystrophy.

Answer 11

1. pure

2. mixed

Question 12

A disease characterized by inability to mineralize (form hydroxylapatite crystals within) OSTEOID SEAMS. these patients have osteoblasts and can synthesize osteoid, but they mineralize inefficiently or not at all.
_____ occurs in children with open growth plates (epiphyses)
_____ occurs in adults with closed epiphyses

Answer 12

1. rickets

2. osteomalacia

Question 13

Osteomalacia & Rickets:
This fundamental inability to mineralize osteooid results in the accumulation of the characteristic _______ seen on a ______.

Answer 13

thickened osteoid seams seen on a bone biopsy

Question 14

What is also characteristic of both rickets and osteomalacia that can be seen by the physician?

Answer 14

deficient mechanically, which leads to 
Bone pain
Pseudofractures
fractures
bowing of the long bones
and other skeletal abnormalties

Question 15

What are some other manifestations of rickets (children) due to the inability to mineralize the growth plate?

Answer 15

• bulbous knobby deformities of the knee, ankles, and costochondral junctions (the *RACHITIC ROSARY), and dental abnormalities.
• rickets also shows gross defects in epiphyseal mineralization and compensatory increases in size of the joints and periarticular bone

Question 16

What are the characteristic radiologic signs of Osteomalacia and Rickets?

Answer 16

• Osteomalacia = Looser zones or Milkman pseudofractures
• Rickets = gross defects in epiphyseal mineralization and compensatory increases in size of joints and perarticular bone

Question 17

Osteomalacia and Rickets pathophysiologic mechanism is caused by a failure of mineralization. These disorders result from an inability to form hydroxyapatite (calcium phosphate) crystals in osteoid, the nonmineralized phase of bone. This inability may results from WHAT?

Answer 17

1. hypophosphemia (common cause)
2. a deficiency of calcium (extremely rare)
3. deficiency of vitamin D (common cause)
4. presence of toxins that interfere with mineralization, such as albumin
5. incompletely defined inhibitors of mineralization in uremic plasma
6. Long term high dose anticonvulsant use

Question 18

REVIEW: u should know this from chapter 73
Finally, because calcium salts are acid soluble, ______ (as occurs with the chronic bicarbonate wasting seen in patients with ureteral implants into ileal conduits) can result in osteomalacia or rickets. Thus, the causes of these mineralization disorders are, in essence, *vitamin D disorders (malabsorption, liver disease), *hypophosphatemic disorders (X-linked hypophosphatemic rickets, autosomal dominant hypophosphatemia, and oncogenic osteomalacia), *metabolic disorders, *drug related disorders, *genetic conditions (vitamin D-dependent rickets I & II, and hypophosphatasia) —all of this is in chapter 73

Answer 18

chronic metabolic acidosis

Question 19

The diagnosis is suggested in the setting of low bone mass, the characteristic radiologic signs noted previously, or unexplained bone pain or weakness. The diagnosis of Osteomalacia and rickets is supported by demonstrating what???

Answer 19

• -supported with = reductions in plasma 25-hydroxyvitamin D or its active form 1,25[OH]2D, hypophosphatemia, or increases in alkaline phosphatase
• -diagnosis can be confirmed with = undecalcified bone biopsy, following oral double tetracycline labeling techniques, which are used to quantitate the degree of failure of mineralization.

Question 20

______ = a collection of disorders that in moderate to severe forms leads to bone pain, pathologic fractures, and demineralization, all occuring in the setting of end stage renal disease or dialysis.

Answer 20

Renal Osteodystrophy

Question 21

HERE COMES A LONG ONE! lol

Can you describe the pathophysiology occuring with renal osteoystrophy?

Answer 21

-the syndrome includes pure secondary hyperparathyroidism, occurring as a result of defective renal production of 1,25[OH]2D combined with an increase in serum phosphate, which leads to hypocalcemia! :) as a result of reduced intestinal calcium absorption and calcium phosphate precipitation into soft tissues, respectively.
This circumstance, in turn, evokes a severe increase in PTH secretion that then causes dramatic increases in bone turnover, demineralization, and fracture.

Question 22

• Patients with renal osteodystrophy may respond dramatically to oral or parental replacement of 1,25[OH]2D and the calcium receptor agonist cinacalcet.
• Other patients with renal osteodystrophy have adequately controlled serum calcium and phosphate, and therefore PTH, as a result of adequate oral calcium supplementation and phosphate binders, but they display _______.

Answer 22

severe osteomalacia (bone pain, reduced bone mineral density on DXA or bone biopsy, and thickened osteoid seams on bone biopsy with a mineralization defect apparent from tetracycline labeling).

Question 23

Other patients with renal osteodystrophy have combinations of secondary hyperparathyroidism and osteomalacia; still others have _____ or ______ = intended to describe patients on dialysis who have the opposite of secondary hyperparathyroidism and osteomalacia: little or no osteoblastic activity, osteoid, or osteoclastic activity.

Answer 23

Low Turnover or Aplastic Bone Disease

• ** The condition may result from inhibitors of bone turnover, such as aluminium intoxication in the past; from excessive treatment with 1,25[OH]2D with suppression of PTH, causing low bone turnover; or form as yet unidentified causes.
• **VERY IMPORTANT TO UNDERSTAND :)

Question 24

The most common genetic disease causing reductions in bone mass due to a mutation in collagen I gene = ________

Answer 24

osteogenesis imperfecta

Question 25

_____ is due to a mutation in the tissue non-specific alkaline phosphate gene. these patients display demineralization, fracture, and bone pain and have little or no measurable alkaline phosphatase.

Answer 25

hypophosphatasia

Question 26

In the past several years, a new genetic disorder has been defined, called the ________ . The disorder is due to inactivating mutations in the low-density lipoprotein-related protein 5 (LRP5) gene and, although very rare, is particularly interesting because activating mutations in the same gene have been show recently to lead to an autosomal dominant form of very high bone mass.

Answer 26

Osteoporosis - pseudoglioma syndrome (severe autosomal dominant osteoporosis with blindness)

Question 27

Patients who have undergone or are undergoing organ transplantation commonly have severe osteoporosis. In some patients, this condition is due to treatment with _______.

Answer 27

immunosuppressive drugs, such as
Glucocorticoids, tacrolimus, or cyclosporine (all of which are potent inhibitors of bone formation and regularly lead to reductions in bone mass.

Question 28

Treatment:
Primary and tertiary hyperparathyroidism?
Osteomalacia and rickets?
Secondary hyperparathyroidism?

Answer 28

1. primary and tertiary hyperparathyroidism = surgical resection of the affected parathyroid tissue
2. Osteomalacia & rickets = replacement drug therapy (vitamin D, calcium, or phosphate) or the offending agent (anticonvulsants) is removed.
3. Secondary Hyperparathyroidism =
   - patient on dialysis = combination of active form of vitamin D, calcium supplementation, phosphate binders, and cinacalcet, depending on clinical situation,
   * **The MOST IMPORTANT THERAPEUTIC POINT IS THAT THESE DISORDERS are COMMONLY AMENDABLE to treatment and can have dramatic and satisfying responses to therapy.
   - the stumbling block = is that these diagnoses are commonly never considered, and the DXA report of osteoporosis is passively accepted and never investigated :( NOT GOOD.. when a patient is diagnosed with osteoporosis … eliminate these disorders before finalizing decision :)