Alendronic Acid; Uses, Side Effects, Interactions, Pragnancy

Alendronic Acid is a second generation bisphosphonate and synthetic analog of pyrophosphate with anti-bone-resorption activity. Alendronic acid binds to and inhibits the activity of farnesyl pyrophosphate synthetase, an enzyme involved in terpenoid biosynthesis. Inhibition of this enzyme prevents the biosynthesis of isoprenoid lipids, donor substrates of farnesylation and geranylgeranylation during the post-translational modification of small GTPase signaling proteins, which are important in the process of osteoclast turnover. As a result, bone resorption and turnover are reduced.

Similar to other bisphosphonates, alendronate has a high affinity for bone mineral and is taken up during osteoclast resorption. Alendronate inhibits farnesyl pyrophosphate synthetase, one of the enzymes in the mevalonic acid pathway involved in producing isoprenoid compounds that are essential for post-translational modification of small guanosine triphosphate (GTP)-binding proteins, such as Rho, Ras, and Rab.

Mechanism of Action of Alendronic Acid

The action of Alendronate on bone tissue is based partly on its affinity for hydroxyapatite, which is part of the mineral matrix of bone. Alendronate also targets farnesyl pyrophosphate (FPP) synthase. Nitrogen-containing bisphosphonates (such as pamidronate, alendronate, risedronate, ibandronate, and zoledronate) appear to act as analogs of isoprenoid diphosphate lipids, thereby inhibiting FPP synthase, an enzyme in the mevalonate pathway. Inhibition of this enzyme in osteoclasts prevents the biosynthesis of isoprenoid lipids (FPP and GGPP) that are essential for the post-translational farnesylation and geranylgeranylation of small GTPase signaling proteins. This activity inhibits osteoclast activity and reduces bone resorption and turnover. In postmenopausal women, it reduces the elevated rate of bone turnover, leading to, on average, a net gain in bone mass.

or

Alendronate (alendronate sodium hydrate) is a nitrogen-containing bisphosphonate, which combines with the bone surface and reduces osteoclast-mediated bone resorption. It is a third-generation bisphosphonate compound, specifically distributed on the surface of bone resorption and taken into osteoclasts. Under the closed circumstances which is formed with osteoclast and the bone surface, alendronate becomes detached from the bone surface and taken into osteoclast since acid released from osteoclast leads to pH decrease (acidified). The uptaken alendronate blocks the pathway of mevalonic acid synthesis, which is a cholesteric synthesis, inhibits the prenylation of GTP binding protein, and decreases the osteoclast’s function by influencing the cytoskeleton. This restraint of alendronate in bone resorption against osteoclasts is reversible, showing no cytotoxicity at more than hundredfold concentration level at which action occurs.

Indications of Alendronic Acid

• Prevention of osteoporosis
• Paget’s disease
• For the treatment and prevention of osteoporosis in women and Paget’s disease of bone in both men and women.
• Treatment of postmenopausal osteoporosis, to reduce the risk of vertebral fractures.
• Treatment of established postmenopausal osteoporosis, to reduce the risk of hip fractures.
• Norse Combi D and associated names are only intended for use in assessed patients for whom the amount of calcium and vitamin D3 included is considered to provide adequate supplementation.
• Treatment of postmenopausal osteoporosis in patients at risk of vitamin D insufficiency.
• It reduces the risk of vertebral and hip fractures.
  is indicated for the treatment of postmenopausal osteoporosis in women at risk of vitamin D insufficiency.It reduces the risk of vertebral and hip fractures.
• Treatment of osteoporosis in post-menopausal women to prevent fractures
• Treatment of osteoporosis in men to prevent fractures
• Prevention and treatment of corticosteroid-induced osteoporosis and prevention of bone loss in post-menopausal women considered at risk of developing osteoporosis.
• Prophylaxis and treatment of female osteoporosis
• Bone destruction
• Prevention and treatment of corticosteroid-associated osteoporosis together with supplements of calcium and vitamin D
• Treatment for osteogenesis imperfecta in patients of 18 years or older
• Dental implants coating (experimental)
• Treatment for osteogenesis imperfecta in patients of 18 years or older
• Dental implants coating (experimental)
• Osteoporosis caused by glucocorticoid
• Osteogenesis Imperfecta
• Osteoporosis caused by glucocorticoid
• Bone destruction

Therapeutic? Indications

• Alendronate sodium tablets are indicated for the treatment of osteoporosis, alendronate sodium tablets increase bone mass and reduce the incidence of fractures, including those of the hip and spine (vertebral compression fractures).
• Osteoporosis may be confirmed by the finding of low bone mass (for example, at least 2 standard deviations below the premenopausal mean) or by the presence or history of osteoporotic fracture?.
• Alendronate sodium tablets are indicated for the prevention of osteoporosis, alendronate sodium tablets may be considered in postmenopausal women who are at risk of developing osteoporosis and for whom the desired clinical? outcome is to maintain bone mass and to reduce the risk of future fracture.
• Alendronate sodium tablets are indicated for treatment to increase bone mass in men with osteoporosis.
• Alendronate sodium tablets are indicated for the treatment of glucocorticoid-induced osteoporosis in men and women receiving glucocorticoids in a daily dosage? equivalent to 7.5 mg or greater of prednisone and who have low bone mineral density. Patients treated with glucocorticoids should receive adequate amounts of calcium and vitamin D.
• Alendronate sodium treatment is indicated in patients with Paget’s disease of bone having alkaline phosphatase at least two times the upper limit of normal, or those who are symptomatic, or those at risk for future complications from their disease.

Contra-Indications of Alendronic Acid

• Acute inflammations of the gastrointestinal tract (esophagitis, gastritis?, ulcerations)
• Clinically manifest osteomalacia
• Certain malformations and malfunctions of the esophagus (strictures, achalasia)
• Inability to stand, walk, or sit for 30 minutes after oral administration
• Renal impairment with a creatinine clearance below 30ml/min
• Hypersensitivity to alendronate or another ingredient
• Hypocalcemia
• Pregnancy and breastfeeding
• Patients below 18 yrs. of age, as no clinical data exists
• Signs of colic, which is usually self-limiting, occurs in 30-45% of horses.
• Tachycardia?
• Electrolyte disturbances – primarily calcium, magnesium, and potassium, which can last for several hours. Caution should be used in horses with disease processes that could be affected by electrolyte disturbances, such as hyperkalemic periodic paralysis? or cardiac disease.
• Kidney damage – it is eliminated by the kidney? and is not recommended for use in animals with impaired renal? function.
• Less serious reactions include stiffness of the neck, decreased appetite, fever, and increased urination.
• Inability to stand, walk, or sit for 30 minutes after oral administration
• Renal impairment with a creatinine clearance below 30ml/min
• Hypocalcemia
• Pregnancy and breastfeeding

The dosage of Alendronic Acid

Strengths: 5 mg, 10 mg,

Prophylaxis of osteoporosis in women

• 5–10 mg daily or 35–70 mg weekly.

Therapy of osteoporosis in women and men 

• 10 mg daily or 70 mg weekly.

Osteoporosis under corticosteroids

• 5–10 mg daily or 35–70 mg weekly in men and premenopausal women or those receiving concomitant HRT.
• In postmenopausal women not receiving HRT, the recommended dose is 10 mg daily or 70 mg weekly.

Paget’s disease

• 40 mg daily for 6 months.

The risk of esophageal irritation places special requirements on how this oral drug is taken. The patient should take the drug only upon rising for the day with 8 oz. of water, and stand, walk, or sit, and remain fasting for 30–45 minutes afterward (preferably 1–2 hours), then eat breakfast. No other medications should be taken for this time. Lying down or reclining after taking the drug and prior to eating breakfast may cause gastroesophageal reflux and esophageal irritation.

Side Effects of Alendronic Acid

The most common

• Heartburn
• The most common (a burning feeling in the chest, behind the breastbone or gullet)
• Abdominal or stomach pain
• pain, warmth and/or swelling in a leg or in the pelvis?
• sudden tingling or coldness in an arm or leg
• Burning, itching, stinging, redness, or other sign of irritation at the application site ,rash
• Indigestion
• Constipation
• High blood pressure
• Nausea, vomiting,
• painful or swollen gums
• numbness or heavy feeling in the jaw
• dull, aching pain in the hip, groin, or thigh
• liver problems,
• stomach pain,
• Dizziness
• a headache,
• reversible hair loss or thinning, and
• fever.

Common

• chills or fever
• a headache, severe? and throbbing
• joint or back pain
• muscle aching or cramping
• muscle pains or stiffness
• chest pressure or squeezing pain in the chest
• excessive sweating
• sudden drowsiness or need to sleep
• sharp pain when taking a deep breath
• coughing up blood
• rust colored urine
• liver problems–nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice? (yellowing of the skin or eyes)
• decreased amount of urine

Rare

• Anxiety
• change in vision
• chest pain or tightness
• confusion
• a cough
• Agitation
• arm, back, or jaw pain
• blurred vision
• chest pain or discomfort
• convulsions
• extra heartbeats
• hallucinations
• a headache
• irritability
• lightheadedness
• muscle pain or cramps
• muscle spasm or jerking of all extremities
• severe pain? in your upper stomach spreading to your back, nausea and vomiting;

Pregnancy & Lactation of Alendronic Acid

FDA Pregnancy Catagory  D