Strontium-Containing Compounds for Use in the Prevention or Treatment of Necrotic Bone Conditions

Abstract

A method for the treatment and/or prophylaxis of an ostenonecrotic bone disease in a mammal in need thereof, such as, e.g., idiopathic or secondary osteonecrosis, avascular bone necrosis, glucocorticoid induced bone ischemia/osteonecrosis, Legg-Calve-Perthes disease and femoral head necrosis, the method comprising administering an effective dose of a strontium-containing compound (a) to the mammal. A method for the treatment and/or prophylaxis of an osteonecrotic bone disease, such as, e.g., idiopathic or secondary osteonecrosis, avascular bone necrosis, glucocorticoid induced bone ischemia/osteonecrosis and femoral head necrosis, in a mammal who is to be or is treated with a therapeutic agent (b) known to or suspected of inducing apoptosis and/or necrosis of bone cells, the method comprising administering a strontium-containing compound (a) in combination with (b).

1 . A method for the treatment and/or prophylaxis of an osteonecrotic bone disease in a mammal in need thereof, the method comprising administering an effective dose of a strontium-containing compound to the mammal. 
   
   
       2 . A method according to  claim 1 , wherein the daily dose of strontium is at least about 0.01 g. 
   
   
       3 . A method according to  claim 1 , wherein the administration takes place one or more times daily. 
   
   
       4 . A method according to  claim 3 , wherein the administration takes place from 2-5 times daily. 
   
   
       5 . A method according to  claim 1 , wherein the administration is by an enteral or parenteral route or by topical administration. 
   
   
       6 . A method according to  claim 5 , wherein the administration is by an oral route. 
   
   
       7 . A method for the treatment and/or prophylaxis of an osteonecrotic bone disease, in a mammal who is to be or is treated with a therapeutic agent known to or suspected of inducing apoptosis and/or necrosis of bone cells, the method comprising administering a strontium-containing compound in combination with the therapeutic agent. 
   
   
       8 . A method according to  claim 7 , wherein the apoptosis and/or necrosis of bone cells lead to an osteonecrotic bone disease. 
   
   
       9 . A method according to  claim 7 , wherein the administration of the strontium-containing compound and the therapeutic agent leads to at least one of the following:
 i) reduction in the incidence or severity of the osteonecrotic bone disease, wherein the incidence or severity of the osteonecrotic bone disease is reduced by at least 5%, in patients treated with the strontium-containing compound and the therapeutic agent in combination as compared to patients treated with the therapeutic agent alone in the same dose as the therapeutic agent in the combination,   ii) reduction of frequency and/or magnitude of side-effects of the therapeutic agent, wherein side effects are being defined as any clinical relevant observation pertaining to the disease or condition in the patient, and wherein the frequency and/or magnitude of the side-effects is reduced by at least 5%, in patients treated with the strontium-containing compound and the therapeutic agent in combination as compared to patients treated with the therapeutic agent alone in the same dose as the therapeutic agent in the combination.   
   
   
       10 . A method according to  claim 7 , wherein the therapeutic agent is a glucocorticoid and/or another steroid hormone. 
   
   
       11 . A method according to  claim 7 , wherein the therapeutic agent is an anti-retroviral compound. 
   
   
       12 . A method according to  claim 7 , wherein the therapeutic agent is a bisphosphonate. 
   
   
       13 . A method according to  claim 7 , wherein the daily dose of strontium is at least about 0.01 g. 
   
   
       14 . A method according to  claim 7 , wherein the strontium-containing compound and the therapeutic agent are administered as a single composition. 
   
   
       15 . A method according to  claim 7 , wherein the strontium-containing compound and the therapeutic agent are administered as separate compositions. 
   
   
       16 . A method according to  claim 7 , wherein the administration of the strontium-containing compound and the therapeutic agent take place simultaneously or sequentially. 
   
   
       17 . A method according to  claim 1 , wherein the strontium-containing compound is selected from the group consisting of strontium salts of an organic or an inorganic acid. 
   
   
       18 . A method according to  claim 17 , wherein the salt is in hydrate, anhydrous, solvate, polymorphous, amorphous, crystalline, microcrystalline or polymeric form. 
   
   
       19 . A method according to  claim 1 , wherein the strontium-containing compound is strontium chloride, strontium carbonate, strontium citrate, strontium malonate, strontium succinate, strontium fumarate, strontium ascorbate, strontium pyruvate, strontium L-glutamate, strontium D-glutamate, strontium L-aspartate, strontium D-aspartate, strontium alpha-ketoglutarate, strontium lactate, strontium tartrate, strontium glutarate, strontium maleate, strontium methanesulfonate, strontium benzenesulfonate, strontium ranelate or mixtures thereof. 
   
   
       20 . (canceled) 
   
   
       21 . (canceled) 
   
   
       22 . A pharmaceutical composition comprising a strontium-containing compound, and a therapeutic agent that is known to or suspected of inducing apoptosis and/or necrosis of bone cells leading to an osteonecrotic bone condition. 
   
   
       23 . A kit comprising two or more components, the first component comprising a strontium-containing compound and the second component comprising a therapeutic agent that is known to or suspected of inducing apoptosis and/or necrosis of bone cells leading to an osteonecrotic bone condition. 
   
   
       24 . The method according to  claim 1 , wherein the osteonecrotic bone disease is idiopathic or secondary osteonecrosis, avascular bone necrosis, glucocorticoid induced bone ischemia/osteonecrosis, Legg-Calve-Perthes disease or femoral head necrosis. 
   
   
       25 . The method according to  claim 7 , wherein the osteonecrotic bone disease is idiopathic or secondary osteonecrosis, avascular bone necrosis, glucocorticoid induced bone ischemia/osteonecrosis and femoral head necrosis. 
   
   
       26 . The method according to  claim 9 , wherein the side effects pertain to bone-pain, joint-pain, immobility, functional impairment, weight loss or bone mineral density (BMD) decrease. 
   
   
       27 . The method according to  claim 11 , wherein the anti-retroviral compound is efavirenz (Sustiva®), zidovudine (Retrovir®), lamivodine (Epivir®), abacavir (Ziagen®), zalcitabine (Hivid®), didanosine (Videx®), stavudine (Zerit®), tenofovir disoproxil fumarate (Viread®), emtricitabine (Emtriva®), fosamprenavir (Lexiva®), nevirapine (Viramune®), delavirdine (Rescriptor®), capravirine, enfuvirtide (Fuzeon®), saquinavir (Invirase®, Fortovase®), ritonavir (Norvir®), indinavir (Crixivan®), tipranavir, amdoxovir, elvucitabine, atazanivir (Reyataz®), nelfinavir (Viracept®), amprenavir (Agenerase®), PRO-542, TMC-114, TMC-125, BMS-56190, or DPC-0830. 
   
   
       28 . The pharmaceutical composition according to  claim 22 , further comprising one or more pharmaceutically acceptable excipients.