Biomaterial Database

Phenytoin and sodium valproate but not levetiracetam induce bone alterations in female mice. 2014

Md Jamir Anwar, and K V Radhakrishna, and Divya Vohora

a Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, Hamdard University, New Delhi 110062, India.

Adverse effects on the bone are amongst the potentially adverse clinical consequences with antiepileptic drugs (AEDs). This study compared the effects of 3 AEDs (phenytoin (PHT), sodium valproate (SVP), and levetiracetam (LTM)) on the bones of a Swiss strain of albino female mice. Drugs were administered daily for 4 months at doses that produced plasma concentrations corresponding to the clinically relevant therapeutic ranges. PHT and SVP (but not LTM) significantly lowered the bone mineral density (BMD) of lumbar vertebrae (L2-L4) as evaluated by dual-energy X-ray absorptiometry (DEXA) scan. The findings were supported by histopathology of vertebral (lumbar) bone and analysis of bone turnover markers. While both PHT and SVP reduced alkaline phosphatase (ALP) and hydroxyproline (HxP) in lumbar vertebrae, and elevated tartarate-resistant acid phosphatase (TRAP) and urinary excretion of calcium, LTM did not affect any of these markers of bone turnover, indicating that the drug might be a safer option in female epileptic patients prone to bone changes.

UI	MeSH Term	Description	Entries
D007527	Isoenzymes	Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.	Alloenzyme,Allozyme,Isoenzyme,Isozyme,Isozymes,Alloenzymes,Allozymes
D008159	Lumbar Vertebrae	VERTEBRAE in the region of the lower BACK below the THORACIC VERTEBRAE and above the SACRAL VERTEBRAE.	Vertebrae, Lumbar
D010672	Phenytoin	An anticonvulsant that is used to treat a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs.	Diphenylhydantoin,Fenitoin,Phenhydan,5,5-Diphenylhydantoin,5,5-diphenylimidazolidine-2,4-dione,Antisacer,Difenin,Dihydan,Dilantin,Epamin,Epanutin,Hydantol,Phenytoin Sodium,Sodium Diphenylhydantoinate,Diphenylhydantoinate, Sodium
D010889	Piracetam	A compound suggested to be both a nootropic and a neuroprotective agent.	2-Pyrrolidone-N-Acetamide,Avigilen,Axonyl,Cerebroforte,Cerepar N,Ciclofalina,Cuxabrain,Dinagen,Gabacet,Geram,Memo-Puren,Nootrop,Nootropil,Nootropyl,Normabraïn,Piracebral,Piracetam AbZ,Piracetam-RPh,Piracetrop,Pirazetam,Pyracetam,Pyramem,Sinapsan,UCB-6215,Memo Puren,Piracetam RPh,UCB 6215,UCB6215
D002118	Calcium	A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.	Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D005260	Female		Females
D006909	Hydroxyproline	A hydroxylated form of the imino acid proline. A deficiency in ASCORBIC ACID can result in impaired hydroxyproline formation.	Oxyproline,4-Hydroxyproline,cis-4-Hydroxyproline,4 Hydroxyproline,cis 4 Hydroxyproline
D000071681	Tartrate-Resistant Acid Phosphatase	One of several acid phosphatases in humans, other mammals, plants, and a few prokaryotes. The protein fold of tartrate-resistant acid phosphatase (TRAP) resembles that of the catalytic domain of plant purple acid phosphatase and other serine/threonine-protein phosphatases that also contain a metallophosphoesterase domain. One gene produces the various forms which include purple acid phosphatases from spleen and other tissues. Tartrate-resistant acid phosphatase is a biomarker for pathological states in which it is over-expressed. Such conditions include GAUCHER DISEASE; HODGKIN DISEASE; BONE RESORPTION; and NEOPLASM METASTASIS.	AcPase V,Acid Phosphatase V,TRAP Type 5 AcPase,TRAcP,Tartrate-Resistant Acid Phosphatase Type 5,Type 5 Acid Phosphatase,Uteroferrin,Acid Phosphatase, Tartrate-Resistant,Phosphatase V, Acid,Phosphatase, Tartrate-Resistant Acid,Tartrate Resistant Acid Phosphatase,Tartrate Resistant Acid Phosphatase Type 5,V, AcPase,V, Acid Phosphatase
D000077287	Levetiracetam	A pyrrolidinone and acetamide derivative that is used primarily for the treatment of SEIZURES and some movement disorders, and as a nootropic agent.	Etiracetam,Etiracetam, (R)-,Etiracetam, R-isomer,Etiracetam, S-isomer,Keppra,UCB 6474,UCB-6474,Ucb L059,Ucb L060,Ucb-L059,Ucb-L060,alpha-ethyl-2-oxo-1-Pyrrolidineacetamide,Etiracetam, R isomer,Etiracetam, S isomer,R-isomer Etiracetam,S-isomer Etiracetam,UCB6474,UcbL060,alpha ethyl 2 oxo 1 Pyrrolidineacetamide
D000135	Acid Phosphatase	An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.2.	Acid beta-Glycerophosphatase,Acid beta Glycerophosphatase