CLINICAL PHARMACOLOGY
Didronel acts primarily on bone. It can inhibit the formation,
growth, and dissolution of hydroxyapatite crystals and
their amorphous precursors by chemisorption to calcium
phosphate surfaces. Inhibition of crystal resorption occurs
at lower doses than are required to inhibit crystal growth.
Both effects increase as the dose increases.
Didronel is not metabolized. The amount of drug absorbed
after an oral dose is approximately 3%. In normal subjects,
plasma half-life of etidronate, based on non-compartmental
pharmacokinetics is 1 to 6 hours. Within 24 hours, approximately
half the absorbed dose is excreted in urine; the remainder
is distributed to bone compartments from which it is slowly
eliminated. Animal studies have yielded bone clearance
estimates up to 165 days. In humans, the residence time
on bone may vary due to such factors as specific metabolic
condition and bone type. Unabsorbed drug is excreted intact
in the feces. Preclinical studies indicate etidronate
disodium does not cross the blood-brain barrier.
Didronel therapy does not adversely affect serum levels
of parathyroid hormone or calcium.
Paget’s Disease
In Paget’s disease of bone (osteitis deformans)
is an idiopatic, progressive disease characterized by
abnormal and accelerated bone metabolism in one or more
bones. Signs and symptoms may include bone pain and/or
deformity, neurologic disorders, elevated cardiac output
and other vascular disorders, and increased serum alkaline
phosphatase and/or urinary hydroxyproline levels. Bone
fractures are common in patients with Paget’s disease.
Didronel slows accelerated bone turnover (resorption
and accretion) in pagetic lesions and to a lesser extent,
in normal bone. This has been demonstrated histoloically,
scintigraphically, biochemically, and through calcium
kinetic and balance studies. Reduced bone turnover is
often accompanied by symptomatic improvement, including
reduced bone pain. Also, the incidence of pagetic fractures
may be reduced, and elevated cardiac output and other
vascular disorders may be improved by Didronel therapy.
Heterotopic Ossification
Heterotopic ossification, also referred to as myositis
ossificans (circumscripta, progressiva or traumatica),
ectopic calcification, periarticular ossification, or
paraosteoarthropathy, is characterized by metaplastic
osteogenesis. It usually presents with signs of localized
inflammation or pain, elevated skin temperature, and redness.
When tissues near joints are involved, functional loss
may also be present.
Heterotopic ossification may occur for no known reason
as in myositis ossificans progressiva or may follow a
wide variety of surgical, occupational, and sports trauma
(e.g. hip arthroplasty, spinal cord injury, head injury,
burns, and severe thigh bruises). Heterotopic ossification
has also been observed in non-traumatic conditions (e.g.
infections of the central nervous system, peripheral neuropathy,
tetanus biliary cirrhosis, Peyronie’s disease, as
well as in association with a variety of benign and malignant
neoplasms).
Clinical trials have demonstrated the efficacy of Didronel
in heterotopic ossification following total hip replacement,
or due to spinal cord injury.
- Heterotopic ossification complicating total hip
replacement typically develops radiographically
3 to 4; weeks postoperatively in the pericapsular area
of the affected hip joint. The overall incidence is
about 50%; about one-third of these cases are clinically
significant.
- Heterotopic ossification due to spinal cord injury
typically develops radiographically l to 4 months after
injury. It occurs below the level of injury, usually
at major joints. The overall incidence is about 40%;
about one-half of these cases are clinically significant.
Didronel chemisorbs to calcium hydroxyapatite crystals and
their amorphous precursors, blocking the aggregation, growth,
and mineralization of these crystals. This is thought to
be the mechanism by which Didronel prevents or retards heterotopic
ossification. There is no evidence Didronel affects mature
heterotopic bone.
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