Agents That Affect Bone Mineral Homeostasis
Subclass, Drug Mechanism of Action
Principal Regulators: A single-chain peptide
hormone composed of 84
Parathyroid amino acids
Hormone (PTH)
A secosteroid produced in
the skin from 7-
Vitamin D dehydrocholesterol under
the influence of UV radiation
A single-chain protein with
251 amino acids, including
Fibroblast Growth 24-amino acid leader
sequence
Factor 23 (FGF23) It inhibits 1, 25 (OH)2D
production and phosphate
reabsorption via NaPi2a and
2c
Secondary Regulators: Secreted by the parafollicular
cells of the mammalian
thyroid
Calcitonin A disulfide bond between
position 1 and 7 is essential
for biologic activity
Alter bone mineral
homeostasis by antagonizing
vitamin D-stimulated
intestinal calcium transport,
Glucocorticoids stimulating renal calcium
excretion, and blocking bone
formation
Can prevent accelerated
Estrogens bone loss during the
Effects
Net effect: raises serum
calcium and reduces serum
phosphate
Net effect: raises both serum
and phosphate
Natural form – vitamin D3
(cholecalciferol)
Plant-derived form – vitamin
D2 (ergocalciferol)
Net effect: decreases serum
phosphate
Principal effect: to lower
serum calcium and
phosphate by actions on
bone and kidney
Chronic hypercalcemia of
sarcoidosis, vitamin D
intoxication and certain
cancers may respond within
several days to glucocorticoid
therapy
Principal therapeutic
application: treatment or
Clinical Applications P, T, I
Calcitriol = vitamin D of
choice because it is capable
of raising serum calcium
within 24 to 48 hours
Hypophosphatemia
Proved useful as ancillary
treatment in some patients
Calcimar = salmon calcitonin
available for parenteral and
nasal administration
Malignancies responding Osteoporosis in adults,
best: multiple myeloma, stunted skeletal
related lymphoproliferative development in children
diseases
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 immediate postmenopausal
period and at least
transiently increase bone in
postmenopausal women
Nonhormonal Agents: Analogs of pyrophosphate
Suppress the activity of
osteoclasts in part via
Bisphosphanates inhibition of farnesyl
[Etidronate, Pamidronate, pyrophosphate synthesis
Alendronate, Risendronate,
Tiludronate, Ibandronate,
Zoledronate]
Rank Ligand (RANKL) A fully human monoclonal
Inhibitor: antibody that binds to and
prevents the action of RANKL
Denosumab
Calcium Receptor Calcimimetic
Agonist: The first representative of a
new class of drugs that
Cinacalcet activates the calcium-sensing
receptor (CaSR)
A cytotoxic antibiotic that has
been used clinically for
Plicamycin Paget’s disease and
hypercalcemia
Useful in reducing the
hypercalciuria and incidence
Thiazide Diuretics of urinary stone formation in
subjects with idiopathic
hypercalciuria
Well established as effective
Fluoride for the prophylaxis of dental
caries and previously been
prevention of
postmenopausal
osteoporosis
Oral forms: RIA
(risendronate, ibandronate,
alendronate)
Inhibit bone resorption and
secondarily bone formation
Blocks bone resorption
Postmenopausal
osteoporosis and some
cancers (prostate and breast)
Inhibits PTH secretion
Approved for the treatment
of secondary
hyperparathyroidism in
chronic kidney disease and
for the treatment of
parathyroid carcinoma
Cytotoxic properties of the
drug appear to involve
binding to DNA and
interruption of DNA-directed
RNA synthesis
Osteoporosis
Bone metastases
Hypercalcemia associated
with malignancy
(pamidronate, zoledronate)
Paget’s disease
Osteoporosis
Treatment of excess bone
resorption in patients with
osteoporosis and certain
cancers
Hyperparathyroidism
Last resort for Paget’s
disease
Principal application: reduce
renal calcium excretion
Esophageal and gastric
irritation (major adverse
effect of oral forms), self-
limited flu-like syndrome,
renal deterioration,
adynamic bone, possible RF,
rare osteonecrosis of jaw,
rare subtrochanteric (femur)
fracture
May increase risk of
infections, osteonecrosis of
the jaw, subtrochanteric
fractures, transient
hypocalcemia
Nausea
Sudden thrombocytopenia
followed by hemorrhage
(most dangerous adverse
effects), hepatic and renal
toxicity
Nausea and vomiting,
gastrointestinal blood loss,
arthralgias, arthritis
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 investigated for the
treatment of osteoporosis
Minerals: Block differentiation of Used in Europe for the tx of Osteoporosis Ectopic calcification
osteonecrosis while osteoporosis Osteomalacia
Strontium, promoting their apoptosis Strontium suppresses bone Deficiencies in calcium or
Calcium, thus inhibiting bone resorption and increases phosphate
resorption bone formation Stimulates bone formation
Phosphate Calcium and phosphate are and inhibits bone resorption
required for bone
mineralization
SERM: First of the SERMs to be Inhibits bone resorption Osteoporosis Increased risk of venous
approved for the prevention without stimulating breast or thromboembolism, does not
of osteoporosis endometrial hyperplasia prevent hot flashes
Raloxifene Interacts selectively with It protects against spine
estrogen receptors fractures but not hip
fractures
Hormones: Acts via its cognate G Recombinant PTH 1-34 for Osteoporosis Hypercalcemia,
protein-coupled receptor the tx of osteoporosis hypercalciuria
Teriparatide Stimulated bone turnover
Stimulates bone turnover Postmenopausal Osteoporosis
Calcitonin Suppresses bone resorption osteoporosis Hypercalcemia
Paget’s disease
A potent stimulator of
calcitonin secretion
Pentagastrin suggesting a possible
physiologic relationship
between gastrin and
calcitonin
Management of Nephrotoxicity (patients
Gallium Nitrate hypercalcemia of malignancy should be well hydrated and
Inhibits bone resorption have good renal output)
TOC for the rapid reduction
Saline Diuresis of serum calcium in severe
hypercalcemia
Phosphate First step: rehydration
with saline and diuresis
with furosemide

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Vitamin D, Metabolites,
Analogs:
Cholecalciferol
(D3)
Ergocalciferol (D2)
Calcitriol
Approved for the tx of
secondary hyperthyroidism in
Doxercalciferol patients with chronic kidney
disease
Same
Paricalcitol
Being used to treat psoriasis,
Calcipotriene a hyperproliferative skin
disorder
Is in phase 3 clinical trials in
Eldecalcitol Japan for the tx of
osteoporosis