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*D.M. Ravi Chand,
V.Sheshayamma, V. Lakshmi Kameshwari, T. Chakradhar, K. Vijayal.
*Department of Pharmacology, Osmania Medical
College, Koti, Hyderabad-500095. India.
Address for Correspondence
D.M. Ravi Chand,
Department of Pharmacology, Osmania Medical College,
Koti, Hyderabad-500095. India.
E-Mail: dm_ravi@rediffmail.com |
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Abstract :
J.Orthopaedics 2006;3(2)e7
Introduction:
Osteoporosis
can be defined as a systemic skeletal disease characterized by
low bone mass, microarchitectural deterioration of bone tissue,
and increased bone fragility and susceptibility to fracture.
[1] It
most commonly affects older populations, primarily
postmenopausal women. The goal of pharmacological treatment is
to maintain or increase bone strength, to prevent fractures
throughout the patient’s life, and to minimize
osteoporosis-related morbidity and mortality by safely reducing
the risk of fracture. The medications that have been used most
commonly to treat osteoporosis include calcium and vitamin D,
estrogen (with or without progestin), bisphosphonates, selective
estrogen receptor modulators (SERMs), and calcitonin.
Parathyroid
hormone (PTH) has recently emerged as a popular osteoporosis
treatment. PTH increases bone mass, which results in greater
bone mineral density (BMD). As a PTH derivative, teriparatide
has proved effective in increasing bone formation, augmenting
bone mass, and reducing fracture rates.
Pharmacodynamics:
A strain of Escherichia coli, modified by recombinant DNA
technology, is used to manufacture teriparatide. The drug
contains recombinant human PTH (rhPTH 1-34) and has a
sequence that is identical to that of the 34N-terminal amino
acids (the biologically active region) of the 84-amino acid
human PTH. [2]
PTH can initiate bone turnover by the stimulation of osteoclasts.
This stimulation results in net resorption of bone or directly
activates bone formation by initiating osteoblastic activity.
Pharmacokinetics:
Teriparatide is absorbed extensively after SQ injection; its
absolute bioavailability is approximately 95%, and its half-life
in serum is approximately one hour when it is given by SQ
injection. The metabolism and excretion of teriparatide have not
yet been formally studied, but the peripheral metabolism of PTH
is believed to occur by nonspecific enzymatic mechanisms in the
liver, followed by excretion via the kidneys.
Adverse effects:
The FDA has issued a black-box warning because of the drug’s
association with an increased incidence of osteosarcoma (a
malignant bone tumor) in male and female rats. [3]This effect is
dose dependent and also on the duration of treatment. The other
adverse effects are headache, asthenia, neck pain, hypertension,
angina pectoris, syncope, nausea, constipation, dizziness,
depression, insomnia, vertigo, hyperuricemia, and hypercalcemia.
Drug Interactions:
Teriparatide has no significant drug–drug interactions.But when
co-administrated with intravenous furosemide (20-100) with 40mcg
of teriparatide results in small elevation in serum calcium
levels. [4] Teriparatide causes an increase in serum calcium
which may predispose patients to digitalis toxicity. [5]
Uses:
Treatment of Osteoporosis:Dose-20mcg subcutaneous daily.
Clinical trails:
In a study , PTH was a potent stimulator of
skeletal dynamics in men with idiopathic, low-bone turnover
osteoporosis.[6] In an other study it was found that treatment
of postmenopausal osteoporosis with PTH decreased the risk of
vertebral and nonvertebral fractures; increased vertebral,
femoral, and total-body BMD; and was well tolerated. [7] Some
have demonstrated that weekly injections of PTH stimulated bone
formation in the cortical and trabecular bone, resulting in
positive effects on bone mass and bone structure. [8] In other
study it was shown that that long term, intermittent treatment
with PTH led to the formation of a substantial amount of new
bone.[9]
Conclusion:
The novel PTH
analog, Teriparatide is the newest option for the treatment of
postmenopausal osteoporosis. It is effective when used as a
single agent and in conjunction with bisphosphontes like
alendronate to increase bone density.[10] It is well tolerated
with the most common adverse effects like dizziness and leg
cramps.
Teriparatide has a place in therapy as an
alternative treatment for osteoporosis, although no current
studies have demonstrated its safety or efficacy after two years
of use.
Reference :
-
Kenny A, Prestwood K. Osteoporosis:
Pathogenesis, diagnosis, and treatment in older adults.
Rheum Dis Clin North Am 2000;26(3):569–591.
-
CenterWatch: Clinical Trials Listing Service. Drugs Approved
by the FDA. Available at:
www.centerwatch.com/patient/
drugs/dru812.html. Accessed March 9, 2003.
-
Food and Drug Administration. Blackbox warning: Teriparatide
injection. Available at: www.fda.gov. Accessed August 25,
2003.
-
Forteo® (teriparatide injection) package insert. Indianapolis,
IN: Eli Lilly and Company; November 2002.
-
Marlon Honeywell, et al Teriparatide for Osteoporosis: A
Clinical Review Vol.28.No 11.November 2003:713-716
-
Kurland E, Cosman F, McMahon D, et al. Parathyroid hormone as
a therapy for idiopathic osteoporosis in men. J Clin Endocrinol
Metab 2000;85:3069–3076.
-
Neer RM, Arnaud CD, Zanchetta JR, et al. Effect of parathyroid
hormone (1-34) on fractures and bone mineral density in
postmenopausal women with osteoporosis. N Engl J Med
2001;344(19):1434– 1440.
-
Okimoto N, Tsurukami H, Okazaki, et al. Effects of a weekly
injection of human parathyroid hormone (1-34) and withdrawal
on bone mass, strength, and turnover in mature
ovariectomized rats. Bone 1998;22(5):523–531.
-
Kneissel M, Boyde A, Gasser J. Bone tissue and its
mineralization in aged estrogen-depleted rats after long-term
intermittent treatment with parathyroid hormone (PTH) analog
SDZ PTS 893 or human PTH (1-34). Bone 2001;28(3): 237–250.
-
Skriptiz R, Andreassen TT, Aspenberg P. Strong effect of PTH
(1-34) on regenerating bone. Acta Orthop Scand 2000;
71:619–624.
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