Pharm Bone Mineral Homeostasis

Answer: D
Bisphosphonates, like alendronate, are drugs of choice in osteoporosis. they are incorporated
into the bone matrix and inhibit the activity of osteoclasts in a dose-dependent manner. The
mechanism of this action is still not clear but is presumably related to the stimulation of
osteoclast apoptosis and/or inhibition of some steps of cholesterol biosynthetic pathway that are
important for osteoclast function.
A, B, C, E) (see explanation above)

Teriparatide is a recombinant PTH 1-34, meaning it is a synthetic form of parathyroid hormone that contains the first 34 amino acids of the PTH molecule. It is used to treat osteoporosis by stimulating bone formation and increasing bone mineral density.

Alendronate is a drug that can induce osteoclast apoptosis. This means that it can cause the death of osteoclasts, which are cells responsible for breaking down bone tissue. By inducing osteoclast apoptosis, alendronate helps to slow down bone resorption and maintain bone mineral homeostasis.

Answer: A
Teriparatide is a recombinant PTH 1-34. Eve if PTH can increase both osteoblast and
osteoclast activity, the net effect of excess of PTH is an increase in bone resorption (bone
calcium, phosphate, collagen and proteins decrease). However low and intermittent doses of
PTH increases bone formation (by increasing osteoblast activity) without stimulating bone
resorption. This has lead to the recent approval of teriparatide for the treatment of osteoporosis.
The drug should be reserved should be reserved for those patients with a high risk of fracture,
like in the present case.
B, C) Actually PTH does the opposite.
D) PTH stimulates, not inhibits, osteoclast activity, but this does not occur when therapeutic
doses of teriparatide are given.
E) PTH stimulates, not inhibits, the renal synthesis of calcitriol.

Calcitonin is the drug that is secreted by the parafollicular cells of the thyroid gland.

Intestinal calcium absorption is potently augmented by calcitriol and this seems the main action
that mediates the therapeutic efficacy of calciferols in rickets and in osteomalacia. There is little
evidence that calcitriol directly promotes bone mineralization. Rather is the increased serum
calcium levels that indirectly promotes bone mineralization by decreasing PTH-mediated bone
resorption.
A, B, C, E) (See explanation above)

Answer: C
The current options for the pharmacological therapy of osteoporosis are bisphosphonates,
SERMs, calcitonin, PTH (teriparatide) and estrogens. Bisphosphonates are first line therapy
since they preserve bone mass, can decrease vertebral and hip fractures by > 50% and have
low toxicity. Moreover in this patient:
A) Estrogens are contraindicated because of previous breast cancer.
B) Calcitonin is contraindicated because of a previous severe allergic reaction to a protein.
D) Fluoride is not approved for osteoporosis since the results of this treatment are still
controversial.
E, F) These drugs are contraindicated since they decrease serum calcium levels.

Answer: F
Bisphosphonates are first line therapy for osteoporosis, so adding alendronate to the present
regimen is a rational choice, since the therapy failed to prevent the decrease in bone mass.
A) This option is irrational. Hydrochlorotiazide is useful in osteoporosis since it decreases the
renal excretion of calcium.
B) SERMs are today preferred over estrogens for the therapy of osteoporosis since they do not
increase the risk of breast and endometrial cancer.
C) Calcitonin is less effective than bisphosphonates in the therapy of osteoporosis.
D) The dose of calcium taken by the patient is the standard dose for calcium supplementation in
postmenopausal women. It is quite unlikely that a larger dose may add additional benefit.
E) Glucocorticoid are contraindicated in osteoporosis since they increased bone reabsorption.

Answer: E
When administered by oral route bisphosphonates (mainly alendronate)can cause frequently
esophageal and gastric irritation. Because of this patients are often instructed to take the
medication early in the morning on an empty stomach with a large glass of water and then to
stay upright for 30 minutes in order to reduce the chance of esophageal irritation.
A) Glucocorticoids can cause gastric irritation but they are contraindicated in osteoporosis.
B, C, D) These drugs are used in case of osteoporosis but their risk of esophageal and gastric irritation is very low.

Cinacalcet activates a calcium-sensing receptor on the parathyroid glands.

Answer: E
The symptoms of the patient, together with the high calcium level, the low phosphorus level and
the high parathyroid hormone level are consistent with the diagnosis of primary
hyperparathyroidism. In fact PTH values are elevated in >90% of parathyroid-related causes of
hypercalcemia, undetectable or low in malignancy-related hypercalcemia, and undetectable or
normal in high-bone-turnover causes of hypercalcemia. The approach to medical treatment of
hypercalcemia varies with its severity. Mild hypercalcemia ( hydration. More severe hypercalcemia (13 to 15 mg/dL) must be managed aggressively
because above that level hypercalcemia can be life-threatening and requires emergency
measures. Therefore the more severe the hypercalcemia, the greater the number of combined
therapies that should be used.
The mainstay of treatment, in patients with normal renal function, is to increase renal calcium
excretion with IV saline and furosemide, which inhibits calcium reabsorption in the thick
ascending limb of Henle. Bisphosphonates, which are long-lasting inhibitors of bone resorption,
have become drugs of choice for the antiresorptive treatment of hypercalcemia In addition
calcitonin could be given for its rapid albeit short-lived, blockade of bone resorption. An effect
on serum calcium is observed within 4-6 hours and last 6-10 hours).
A) Calcitriol is contraindicated in this case since it tends to increase serum calcium level. .
B, C) Thiazides are contraindicated since they enhance calcium reabsorption in the distal
convolute tubule. Fluoride stimulate bone formation, but the doses that cause hypocalcemia are
toxic and the drug is not used for this purpose.
D) Potassium sparing diuretics have low efficacy and are contraindicated in this case since they
tend to enhance calcium reabsorption in the distal convolute tubule are

Answer: B
If calcium supplementation is adequate, fluoride can increase bone formation and trabecular
bone volume. However the new bone appear to be structurally abnormal and is associated with
an increased incidence of fractures. For these reasons the use of fluoride in the therapy of
osteoporosis remains controversial.
A, C, D, E) All these drugs tend to decrease, not to increase, new bone formation.

Answer: D
The symptoms and the history of the patient indicate that she is suffering from severe
hypocalcemia secondary to hypoparathyroidism, likely due to accidental damage of parathyroid
glands during thyroidectomy. The treatment of severe hypocalcemia can be best accomplished
with slow infusion of calcium gluconate (the preferred calcium salt for Iv therapy because it is
less irritating for veins.
A) Vitamin D can increase calcium levels but its onsets of action is too slow for an emergency
therapy
B, C, E, F) All these drug are actually contraindicated since they decrease serum calcium
levels.

Answer: C
The symptoms and signs of the patient and the elevated alkaline phosphatase indicated that he
was most likely suffering for hypercalcemia due to bone metastases of prostate cancer.
Rehydration with saline and diuresis with furosemide are the first step of the treatment of severe
hypercalcemia. Bisphosphonates like pamidronate, infused over at least 15 minutes, have been
approved for the acute treatment of hypercalcemia of malignancy.
A) IV sodium phosphate is probably the fastest way to lower serum calcium level, but it is an
hazardous procedure because of the risk involved (sudden hypocalcemia, ectopic calcification,
hypotension, acute renal failure). In light of satisfactory responses to other agents, IV sodium
phosphate cannot be recommended as a mean to treat hypercalcemia Therefore IV phosphate
should be used only after other method of treatment have failed to control hypercalcemia.
B, D, E, F) These drug s are ineffective of contraindicated in case of hypercalcemia.

Answer: A
The symptoms and signs of the patient indicate that he is most likely affected by Paget’s
disease of bone, a chronic disorder of the adult skeleton in which bone turnover is accelerated
in localized areas. Bisphosphonates are first line agents for this disease. Calcitonin an
alternative to bisphosphonates whin this drugs are contraindicated, as in the present case (see
below).
B) Bisphosphonates are relatively contraindicated in patients with gastrointestinal reflux
disease, esophagitis, gastritis and peptic ulcer.
C, D, E, F) These drugs are useless in Paget’s disease.

Answer: A
The symptoms and signs of the patient together with the lab results suggest that he is suffering
from rickets, a disease that can affect children, more often the black ones, since skin
pigmentation makes ultraviolet irradiation more difficult. Rickets is due to vitamin D deficiency
which in turn causes deficient mineralization of epiphyseal cartilages and osteoid matrix.
Vitamin D deficiency tend to cause hypocalcemia. When this occurs PTH production is
increased. Thus the serum level of calcium is restored to nearly normal by hypophosphatemia
persists and so mineralization of bone is impaired. Cholecalciferol (Vit D3) supplementation with
adequate calcium and phosphate intake is the standard therapy for rickets.
B, C, D , E) (see explanation above)

Answer: D
The symptoms, the lab results and the history of the patient indicate that he was most likely
suffering from alcoholic cirrhosis. The bone demineralization and the low calcium levels suggest
that the diffuse liver disease caused an impaired synthesis of 25(OH)D with the final outcome of
osteomalacia. Calcitriol is the most effective agent for hypocalcemia in a patient with impaired
liver function since it bypass the impaired synthesis of the agent.
A) Patients with hypocalcemia have already an increased production of PTH, so teriparatide can
add very little to the therapy.
B) Vit D3 is not effective because the liver cannot provide the 25 hydroxylation.
C, E )(see explanation above)

Answer: C
The high creatinine levels of the patient point out that the patient was most likely suffering from
chronic renal failure, presumably due to diabetic nephropathy (the most common cause of renal
failure in the U.S.). Chronic renal failure can cause renal osteodystrophy, a term used to
describe collectively all the skeletal changes in chronic renal disease. Renal osteodystrophy is
due to several factors which include loss of calcitriol production because the damaged kidney
cannot activate the renal alpha1-hydroxylase which converts 25(OH) D3 into calcitriol. This
contributes to secondary hyperparathyroidism (remember that calcitriol suppresses PTH gene
expression and secretion) which in turn can cause increased bone resorption. In chronic renal
failure calcitriol should be initiated as long as serum phosphate is not significantly elevated.
Paricalcitol, synthetic analog of calcitriol, is preferred when the secondary hyperparathyroidism
is pronounced, like in the present case (see the high serum calcium levels) because it may
lower PTH levels without significantly increasing serum calcium levels.
A, B, D, E) (see explanation above)

Calcitriol is the correct answer because it can inhibit the gene expression of PTH.

Answer: C
The symptoms and signs of the patient indicate that he was most likely affected by plaque
psoriasis, a common skin disorder that affects 1-5% of the population worldwide. The disease is
diagnosed most often by clinical appearance and distribution of lesions. Arthritis develops in up
to 30% of patients, like in the present case (see the swollen and tender joints). Calcipotriene is
a topical vit D 3 analog which induces normal keratinocyte proliferation and differentiation.
Improvement of psoriasis is generally noted following two weeks of therapy, with continued
improvement for up to 8 weeks of treatment.
A) Glucocorticoids, not mineralocorticoids, are used for psoriasis.
B, D, E) (see explanation above)