MENOFOS 70

Indications

• Osteoporosis in postmenopausal women
• Osteoporosis in men
• Paget's disease of bone
• Glucocorticoid-induced osteoporosis

Dosage

Children: Safety and efficacy in children have not been established, thus specific pediatric dosing for alendronate is not available. Refer to the BNF for Children for further guidance.

Adults: For the treatment of osteoporosis, the usual dose is 10 mg once daily or 70 mg once weekly. For Paget's disease, the recommended dose is 40 mg once daily for 6 months.

Mechanism of action

Alendronic acid binds to bone hydroxyapatite. Bone resorption causes local acidification, releasing alendronic acid, which is taken into osteoclasts by fluid-phase endocytosis. This process leads to the apoptosis of osteoclasts, resulting in decreased bone resorption, as evidenced by reduced levels of urinary calcium and collagen degradation products.

Pharmacodynamics

Alendronic acid has very low oral bioavailability and distributes into soft tissues and bone. It does not undergo metabolism and is primarily excreted unchanged in urine. Its effects on bone density become apparent after sustained administration, as it preferentially accumulates at sites of active bone resorption.

Pharmacokinetics

After oral administration, alendronic acid has a very low bioavailability, with most of the drug being absorbed in the gastrointestinal tract. It subsequently distributes to bone and soft tissues. The drug is excreted in urine as unchanged alendronic acid, and it does not undergo significant metabolic transformation.

Adverse effects

• Gastrointestinal irritation
• Osteonecrosis of the jaw
• Atypical femoral fractures
• Abdominal pain
• Constipation
• Diarrhea
• Nausea
• Esophageal irritation
• Headache

Interactions

• aspirin+alendronate: Unknown (increases risk of gastrointestinal irritation)
• nsaids+alendronate: Unknown (increases risk of gastrointestinal irritation)
• oralmagnesium+alendronate: Unknown (decreases absorption)
• oralzinc+alendronate: Unknown (decreases absorption)

Precautions

• Use with caution in patients with renal impairment.
• Monitor for signs of gastrointestinal irritation.
• Assess dental health prior to initiation to minimize risk of osteonecrosis of the jaw.

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Alendronate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether alendronate is excreted in human milk. Caution should be exercised when administering to a nursing woman.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Formulations

• Alendronate sodium 10 mg tablet
• Alendronate sodium 70 mg tablet
• Alendronate sodium 70 mg/75 mL oral solution

Mechanism of action

Alendronic acid binds to bone hydroxyapatite. Bone resorption causes local acidification, releasing alendronic acid which is that taken into osteoclasts by fluid-phase endocytosis. Endocytic vesicles are acidified, releasing alendronic acid to the cytosol of osteoclasts where they induce apoptosis. Inhibition of osteoclasts results in decreased bone resorption which is shown through decreased urinary calcium, deoxypyridinoline and cross-linked N-telopeptidases of type I collagen. Animal studies have indicated the following mode of action. At the cellular level, alendronate shows preferential localization to sites of bone resorption, specifically under osteoclasts. The osteoclasts adhere normally to the bone surface but lack the ruffled border that is indicative of active resorption. Alendronate does not interfere with osteoclast recruitment or attachment, but it does inhibit osteoclast activity. Studies in mice on the localization of radioactive (3)H-alendronate in bone showed about 10-fold higher uptake on osteoclast surfaces than on osteoblast surfaces. Bones examined 6 and 49 days after (3)H-alendronate administration in rats and mice, respectively, showed that normal bone was formed on top of the alendronate, which was incorporated inside the matrix. While incorporated in bone matrix, alendronate is not pharmacologically active. Thus, alendronate must be continuously administered to suppress osteoclasts on newly formed resorption surfaces. Histomorphometry in baboons and rats showed that alendronate treatment reduces bone turnover (i.e., the number of sites at which bone is remodeled). In addition, bone formation exceeds bone resorption at these remodeling sites, leading to progressive gains in bone mass. 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 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. ... The differences that exist among individual BPs in terms of mineral binding and biochemical actions may explain differences in their clinical behavior and effectiveness. The classical pharmacological effects of bisphosphonates (BPs) appear to be the result of two key properties: their affinity for bone mineral and their inhibitory effects on osteoclasts. There is new information about both properties. Mineral binding affinities differ among the clinically used BPs and may influence their differential distribution within bone, their biological potency, and their duration of action. The antiresorptive effects of the nitrogen-containing BPs (including alendronate, risedronate, ibandronate, and zoledronate) appear to result from their inhibition of the enzyme farnesyl pyrophosphate synthase (FPPS) in osteoclasts. FPPS is a key enzyme in the mevalonate pathway, which generates isoprenoid lipids utilized for the post-translational modification of small GTP-binding proteins that are essential for osteoclast function. Effects on other cellular targets, such as osteocytes, may also be important. BPs share several common properties as a drug class. However, as with other families of drugs, there are obvious chemical, biochemical, and pharmacological differences among the individual BPs. Each BP has a uniqu

Pharmacodynamics

Alendronic acid tablets have a very low oral bioavialability. After administration it distributes into soft tissue and bone or is excreted in the urine. Alendronic acid does not undergo metabolism.