Review of Pharmacology - 9E (2015)

Review of Pharmacology
• Long-term use of bisphosphonates increases the risk of atypical ‘chalkstick’ fracture
of femur (subtrochantric or shaft). Risk increases with concurrent high dose steroid
therapy.
• Long-term use of bisphosphonates increase the risk of esophageal cancer.
• Bisphosphonates can result in hypocalcemia as well as hypercalcemia.
• Half-life of alendronate in bone is 10 years.
Endocrinology
254
Distinctive toxicity of bisphosphonates
is esophageal irritation
that can lead to ulceration
as well
Teriparatide and strontium
ranelate can stimulate osteoblast
whereas most other agents used
for osteoporosis act by inhibiting
osteoclast
Note:
• Main contraindications of bisphosphonates are renal dysfunction, esophageal motility disorders
and peptic ulcer.
• Zoledronate infusion of 5mg once yearly has been approved for treatment of osteoporosis.
Selective Estrogen Receptor Modulators
Estrogens inhibit bone resorption directly by inhibiting osteoclasts and indirectly by
modulating paracrine factors. It increases anti-resorptive [IGF-1 and TGF-β] and suppresses
pro-resorptive [IL-1, IL-6, TNF-α and osteocalcin] factor synthesis by osteoblasts.
Estrogen increases bone formation and its deficiency in the old age may result in postmenopausal
osteoporosis. Use of hormone replacement therapy for this condition predisposes
the patients to the adverse effects of estrogens on breast and endometrium (increased incidence
of breast and endometrial carcinoma). Raloxifene is a selective estrogen receptor modulator
with estrogen agonistic action on bone and antagonistic action on breast and endometrium. It
is therefore the preferred drug for the treatment and prevention of post-menopausal osteoporosis.
Major adverse effect of this agent is increased risk of thromboembolism. Bazedoxifene
is another SERM that has been approved recently for prevention of post menopausal
osteoporosis and to treat vasomotor symptoms of menopause.
Teriparatide
Teriparatide and strontium ranelate can stimulate osteoblast whereas most other agents used
for osteoporsis act by inhibiting osteoclast
It is recombinant PTH 1-34
. It has been noted that PTH in low and pulsatile dose stimulates
bone formation whereas in excess it causes resorption of bones. Teriparatide is available for
the treatment of osteoporosis by intermittent s.c. administration.
• Teriparatide stimulates the production of new collagenous bone matrix that must
be mineralized. Therefore, patients receiving teriparatide must have sufficient
intake of vitamin D and calcium.
• When administered to patients with osteoporosis in doses of 20 mcg/d
subcutaneously for 2 years, Teriparatide dramatically improves bone density in
most bones except the distal radius.
• The recommended dose should not be exceeded, since Teriparatide has caused
osteosarcoma in rats when administered in very high doses. Due to potential risk
of osteosarcoma, teriparatide should be avoided in:
––
Paget's disease of bone
––
Prior radiotherapy to bone
––
Past history of osteo or chondrosarcoma
––
Unexplained increase in alkaline phosphatase
• Teriparatide should be used with caution in patients if they also taking
corticosteroids and thiazide diuretics along with oral calcium supplementation
because hypercalcemia may develop.
• Following a course of Teriparatide, a course of bisphosphonates should be
considered in order to retain the improved bone density.
• Other adverse effects have included exacerbation of nephrolithiasis and elevation
of serum uric acid levels.
• Teriparatide may be used for healing of chalkstick fractures associated with
bisphosphonate therapy.
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