Calcium and Bone Metabolism 2

Question 1

What are the most common causes of secondary hyperparathyroidism?

Answer 1

appropriate elevation in PTH due to vitamin D deficiency or chronic kidney disease

Question 2

How does PTH help to address vitamin deficiency hypocalcemia?

Answer 2

increases Ca mobilization from bone
increases Ca reabsorption in kidney
stimulates the activity of 1a-hydroxylase

Question 3

What are the mechanisms of hypocalcemia in CKD?

Answer 3

renal clearance of phosphate is impaired: phosphate binds free calcium
renal 1a-hydroxylase activity is impaired

Question 4

What other disease states or imbalances will cause secondary hyperparathryoidism

Answer 4

(vit. D deficiency, CKD)

acute pancreatitis
massive blood transfusions
osteoblastic metastases
hungry bone syndrome

Question 5

What is the action of PTH on osteoblasts?

Answer 5

PTH binds to osteoblasts and stimulates expression of RANKL on osteoblasts

binding of RANKL to RANK on osteoclasts to break down bone

PTH also decreases OPG which can bind to RANKL as soluble receptor

Question 6

What cell lines are osteoclasts born from?

Answer 6

hematopoietic

Question 7

What is osteoporosis?

Answer 7

low bone mass and/or micro architectural changes that lead to bone fragility and increased risk of fracture which can be due to failure to achieve peak bone mass or due to bone loss

Question 8

Why is postmenopausal osteoporosis the most common type of osteoporosis encountered in clinical practice?

Answer 8

women lose bone more rapidly then men after menopause and esp. rapidly in the first few years primarily due to accelerated bone turnover in which bone resorption outpaces bone formation

Question 9

What are risk factors for osteoporosis?

Answer 9

female gender
increasing age
postmenopausal status
low weight
Caucasian/Asian descent
smoking
family history

(additional risk for falls- poor muscle strength, impaired balance or vision)

Question 10

What is the strongest risk factor for future low trauma fracture?

Answer 10

previous history of low trauma fracture, these patients are at high risk of more fractures and aggressive risk reduction should be implemented

Question 11

What are the most common fractures associated with osteoporosis?

Answer 11

vertebral compression fractures (most common)- can be painless or painful

hip fractures (high morbidity and mortality)

distal radius fractures

Question 12

What are secondary causes of osteoporosis?

Answer 12

glucocorticoid-induced (meds or Cushing’s)
endocrine issues (low testosterone, hyperthyroidism, hyperparathyroidism)
malignancies: MM, other lymphoproliferative malignancies

Question 13

What are the ill-effects of glucocorticoids on osteoporosis?

Answer 13

decreased intestinal calcium absorption
increased expression of RANKL on osteoblasts
suppress maturation of and induce apoptosis of osteoblasts
increase renal Ca and Phos. losses

Question 14

What are the criteria for diagnosis of osteoporosis.

Answer 14

occurrence of low trauma fracture without alternative explanation (no matter the bone density testing)

in absence of low trauma fracture, a BMD scan

Question 15

Describe the two different scores used to rank osteoporosis.

Answer 15

measured bone mineral density is reported and converted into two standard scores based on comparison with respective reference populations:

T-score- # SD the patient is from mean BMD of sex-matched, YOUNG, healthy controls

Z-score- # of SD the patient is from the mean BMD of sex-matched, AGE-matched population

Question 16

When are Z-scores most useful and when are T-scores most helpful

Answer 16

T-scores are most useful in postmenopausal women and in men over 50y (T-score of -2.5 or lower is osteoporosis and -1.0 to -2.4 means osteopenia/low bone mass); Z-scores should not be used in older individuals

Z-scores are used in premenopausal women and in young men (-2.0 defines ‘lower than expected bone density for age’) and dx of osteoporosis should not be made on the basis of DXA results alone

Question 17

What is osteomalacia?

Answer 17

osteomalacia is a disease of abnormal bone mineralization and when seen in children is called Rickets (before growth plate closure)

specific signs of Rickets includes enlargement of the cartilage at the growth plates of the costochondral junctions and long bones, bowing of long bones of the age

Question 18

What are the ways osteoporosis can be distinguished from osteomalacia?

Answer 18

osteomalacia is usually accompanied by pain and tenderness with muscle weakness (and also increased risk of fracture)

pain is caused by swelling of bone and stretching of periosteium (innervated)

Question 19

What are possible causes of rickets or osteomalacia?

Answer 19

vitamin D deficiency (classic)
pseudo vitamin D deficiency (inactivating mutation of 1a-hydroxylase)
hereditary vitamin D resistant rickets (homozygous defects in VDR
X-linked hypophosphatemic rickets and autosomal dominant hypophophatemic rickets
tumor-induced osteomalacia (tumor producing excess FGF-23 causing renal phos. loss and impaired 1a-hydroxylase)

Question 20

Describe Paget’s disease of the bone the mechanism and clinical signs.

Answer 20

focal lesions of uncontrolled resorption and formation due to hyperactive osteoclastic bone resorption which leads to chaotic osteoblastic activity

presents with elevated alk. phos. and warmth, pain and fracture at lesion sites (can be asymptomatic

(tx. with potent bisphosphonates)

Question 21

Casuses fibrous dysplasia and what are the clinical symptoms?

Answer 21

expanding bone lesions containing fibroblastic and osteoblastic cells caused by somatic mosaicism for a gain of function mutation in Gsa (constitutive action of parathyroid receptors and others)

Question 22

Describe McCune Albright Syndrome.

Answer 22

includes fibrous dysplasia, precocious puberty (ovarian or testicular hyperfunciton without LH/FSH stimulation) and cafe-au-alit spots