The primary target of ibandronate sodium monohydrate is farnesyl pyrophosphate synthase (FDPS), a key enzyme in the mevalonate pathway . By inhibiting FDPS, ibandronate blocks the formation of isoprenoid compounds, thereby inhibiting the farnesylation and geranylgeranylation of small GTPase signaling proteins such as RAS and RHO family members, ultimately inducing osteoclast apoptosis and inhibiting bone resorption . Additionally, ibandronate exhibits high affinity for hydroxyapatite crystals in the bone matrix and selectively adsorbs to bone surfaces, achieving targeted distribution .

Ibandronate (1.25–2 μM) significantly slows the growth of endothelial cells, while ibandronate (2 μM) also slows the formation of capillary-like tubes and speeds up endothelial cell apoptosis. Ibandronate (< 100 μM) increases VEGF expression in endothelial cells in a dose-dependent manner. [1] In a dose-dependent manner, ibandronate (< 100 μM) inhibits the growth of the two prostate cancer cell lines, LNCaP and PC-3. [2]

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In vitro studies demonstrate that ibandronate exhibits anti-angiogenic and anti-tumor activities. Ibandronate (1.25-2 μM) significantly reduces endothelial cell growth, and at 2 μM, significantly reduces capillary-like tube formation while increasing endothelial cell apoptosis . Ibandronate (<100 μM) dose-dependently increases VEGF expression in endothelial cells . In prostate cancer cell lines LNCaP and PC-3, ibandronate (<100 μM) inhibits cell growth in a dose-dependent manner . Furthermore, ibandronate inhibits osteoclast-mediated bone resorption without directly affecting bone mineralization.

Ibandronate significantly lowers the risk of new morphometric vertebral fractures in osteoporotic women after 3 years of treatment when given either daily (2.5 mg) or intermittently (20 mg every other day for 12 doses every 3 months). After three years of treatment, ibandronate significantly and gradually raises the BMD of the lumbar spine in osteoporotic women by 6.5% and 5.7%, respectively, when taken either daily (2.5 mg) or intermittently (20 mg every other day for 12 doses every three months).[3] Ibandronate ( 125 mg/kg s.c.) increases bone mineral density (BMD), trabecular bone volume and number, load to failure (Fmax), and yield load in long bones and vertebrae in ovariectomized rats.Additionally, all doses completely prevent increased trabecular separation in ovariectomized rats. [4]

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In vivo studies demonstrate that ibandronate exhibits significant efficacy in both osteoporosis and bone metastasis models. In osteoporotic women treated for 3 years with either daily 2.5 mg or intermittent dosing (20 mg every other day for 12 doses every 3 months), the risk of new morphometric vertebral fractures was reduced by 62% and 50%, respectively (p=0.0006), while lumbar spine bone mineral density increased by 6.5% and 5.7%, respectively . In ovariectomized rat models, ibandronate (≤125 mg/kg, subcutaneous) dose-dependently increased bone mineral density, trabecular bone volume, and trabecular number, as well as increasing maximum load and yield load in long bones and vertebrae . For patients with hypercalcemia, a single intravenous dose of 2-6 mg significantly reduces serum calcium levels.

Target Enzyme Preparation: Recombinantly express human FDPS in E. coli and purify by affinity chromatography. Radiolabeled Substrate Preparation: Use [¹⁴C]-isopentenyl pyrophosphate as the radiolabeled substrate. Inhibitor Incubation: Pre-incubate varying concentrations of ibandronate sodium (0.1 nM-10 μM) with FDPS enzyme in reaction buffer for 10 minutes. Reaction Initiation and Termination: Initiate the enzymatic reaction by adding substrate, incubate at 37°C for appropriate duration, then terminate. Product Detection: Measure the amount of radioactive product generated by liquid scintillation counting. Data Analysis: Plot concentration-inhibition curves to calculate IC₅₀ and Ki values.

Cell Culture: Culture human umbilical vein endothelial cells or prostate cancer cell lines (LNCaP, PC-3) in medium containing 10% fetal bovine serum at 37°C in a 5% CO₂ incubator. Drug Treatment: Add varying concentrations of ibandronate sodium (e.g., 0.1-100 μM) and incubate for 24-72 hours. Viability Assay: Measure cell viability using MTT or CCK-8 assays to calculate IC₅₀ values. Tube Formation Assay: Seed endothelial cells on Matrigel-coated plates, add ibandronate sodium, and observe capillary-like tube formation after 6-18 hours. Apoptosis Detection: Detect apoptosis rate using Annexin V-FITC/PI double staining by flow cytometry. VEGF Expression Detection: Measure VEGF levels in cell culture supernatants or cell lysates by ELISA or Western blot.

Animal Selection: Use Sprague-Dawley rats or ICR mice; female animals are typically used for osteoporosis studies, with ovariectomy-induced bone loss models. Dosing Regimen: Ibandronate sodium can be administered via oral gavage, intravenous injection, or subcutaneous injection. Common dose ranges are 0.5-125 mg/kg, with daily or intermittent dosing schedules. Efficacy Assessment: Bone Mineral Density Measurement: Measure lumbar spine and femoral BMD using dual-energy X-ray absorptiometry. Bone Turnover Markers: Detect serum osteocalcin, urine C-telopeptides of type I collagen, and other markers by ELISA. Bone Histomorphometry: Collect femurs and vertebrae for tissue sectioning to analyze trabecular bone volume, trabecular number, and trabecular separation. Biomechanical Testing: Perform three-point bending tests to measure maximum load and yield load. Data Analysis: Compare BMD, bone turnover markers, and biomechanical parameters between treatment and model/control groups.

Ibandronate sodium is rapidly absorbed after oral administration with a Tmax of approximately 1.1 hours, but oral bioavailability is very low (approximately 0.63%) with significant interindividual variability, and food can reduce bioavailability by up to 90% . Following intravenous administration, pharmacokinetics are linear and dose-dependent: AUC₀-∞ values for 2 mg and 6 mg groups are 333.4±46.0 and 939.1±267.1 ng·h/mL, with clearances of 6.1 and 6.9 L/h, respectively . Plasma protein binding is very high (85.7-99.5%), with a large volume of distribution (90-368 L) . Ibandronate is not metabolized in the body and is primarily excreted unchanged in the urine (approximately 55%) . The terminal half-life is long (37-157 hours) . Clearance is significantly positively correlated with creatinine clearance (r=0.858), and patients with renal impairment show an approximately 60% increase in AUC .

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

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Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Ibandronate sodium has a low oral absorption rate (average absorption rate of 6% in adults on an empty stomach, and almost no absorption when taken with food), therefore breastfed infants are unlikely to absorb ibandronate sodium. However, since there is currently no information on the use of ibandronate sodium during lactation, other medications may be preferred, especially for breastfed newborns or premature infants.
◉ Effects on Breastfed Infants
No published information found as of the revision date.
◉ Effects on Lactation and Breast Milk
No published information found as of the revision date.

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Ibandronate sodium is generally well-tolerated in clinical studies. The oral LD₅₀ in rats is 811 mg/kg . Common adverse reactions include hypocalcemia, limb pain, back pain, and dyspepsia . Intravenous administration may cause transient decreases in blood calcium levels. Rare but serious adverse reactions include osteonecrosis of the jaw (incidence <1%). Caution should be exercised in patients with renal impairment (creatinine clearance <30 mL/min), as renal impairment can lead to an approximately 60% increase in drug exposure . In multiple myeloma patients, no evidence of acute nephrotoxicity was observed despite compromised baseline renal function . Drug interactions occur with calcium-containing medications, aluminum preparations, and iron, forming non-absorbable complexes . Ibandronate sodium is for research and clinical use only; standard safety practices should be followed during experimental handling.

[1]. Microvasc Res . 2009 Dec;78(3):453-8.

[2]. Acta Oncol . 2011 Jan;50(1):127-33.

[3]. J Bone Miner Res . 2004 Aug;19(8):1241-9.

[4]. J Rheumatol . 2002 Oct;29(10):2200-8.

[5]. Transplantation . 2012 Feb 15;93(3):331-6.

Ibandronate sodium is the sodium salt form of ibandronate, a synthetic nitrogenous bisphosphonate. Ibandronate inhibits farnesyl pyrophosphate synthase, leading to a reduction in geraniol-geraniol GTPase signaling protein and inducing osteoclast apoptosis. This drug increases bone mineral density, reduces bone remodeling, inhibits osteoclast-mediated bone resorption, and alleviates metastasis-related and corticosteroid-related bone pain. Aminobisphosphonates are potent bone resorption inhibitors. They are used to treat hypercalcemia associated with malignancies, prevent fractures and skeletal complications in patients with breast cancer bone metastases, and treat and prevent postmenopausal osteoporosis. See also: Ibandronate sodium (note moved to). Indications: Treatment of osteoporosis in postmenopausal women at increased risk of fracture (see Section 5.1). It has been shown to reduce the risk of vertebral fractures, but its efficacy in femoral neck fractures has not been established.
Bandronate sodium is indicated for: prevention of skeletal events (pathological fractures, skeletal complications requiring radiation therapy or surgery) in patients with breast cancer bone metastases; and treatment of hypercalcemia caused by tumors with or without metastases.
Treatment of hypercalcemia caused by tumors with or without metastases.

C9H24NNAO8P2

359.22

359.087

C, 30.09; H, 6.73; N, 3.90; Na, 6.40; O, 35.63; P, 17.24

138926-19-9

Ibandronic acid;114084-78-5;Ibandronate Sodium;138844-81-2; 114084-78-5 (free acid); 155453-10-4 (sodium hemihydrate); 138926-19-9 (sodium monohydrate)

23663991

Solid powder

587.8ºC at 760 mmHg

84ºC (dec)

309.3ºC

2.88E-16mmHg at 25°C

0.873

5

9

9

21

377

0

OC(P(O)(O)=O)(P(O)([O-])=O)CCN(C)CCCCC.[Na+].O

VBDRTGFACFYFCT-UHFFFAOYSA-M

InChI=1S/C9H23NO7P2.Na.H2O/c1-3-4-5-7-10(2)8-6-9(11,18(12,13)14)19(15,16)17;;/h11H,3-8H2,1-2H3,(H2,12,13,14)(H2,15,16,17);;1H2/q;+1;/p-1

sodium;hydroxy-[1-hydroxy-3-[methyl(pentyl)amino]-1-phosphonopropyl]phosphinate;hydrate

Ibandronate sodium monohydrate; Boniva; Ibandronate sodium monohydrate; 138926-19-9; IBANDRONATE SODIUM; Ibandronate sodium hydrate; BM-21.0955; Ibandronate sodium; Sodium trihydrogen (1-hydroxy-3-(methylpentylamino)propylidene)diphosphonate, monohydrate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O: ~25 mg/mL (~69.6 mM)
DMSO: <1 mg/mL

Solubility in Formulation 1: 25 mg/mL (69.59 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)