CA2685407A1 - Methods and compositions for fostering and preserving bone growth - Google Patents
Methods and compositions for fostering and preserving bone growth Download PDFInfo
- Publication number
- CA2685407A1 CA2685407A1 CA002685407A CA2685407A CA2685407A1 CA 2685407 A1 CA2685407 A1 CA 2685407A1 CA 002685407 A CA002685407 A CA 002685407A CA 2685407 A CA2685407 A CA 2685407A CA 2685407 A1 CA2685407 A1 CA 2685407A1
- Authority
- CA
- Canada
- Prior art keywords
- bone
- subject
- agent
- parathyroid hormone
- calcitonin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims abstract 31
- 230000008468 bone growth Effects 0.000 title claims abstract 4
- 239000000203 mixture Substances 0.000 title 1
- 210000000988 bone and bone Anatomy 0.000 claims abstract 39
- 239000003795 chemical substances by application Substances 0.000 claims abstract 17
- 229940124325 anabolic agent Drugs 0.000 claims abstract 12
- 239000003263 anabolic agent Substances 0.000 claims abstract 12
- 230000003416 augmentation Effects 0.000 claims abstract 8
- 239000000560 biocompatible material Substances 0.000 claims abstract 7
- 239000008280 blood Substances 0.000 claims abstract 7
- 210000004369 blood Anatomy 0.000 claims abstract 7
- 230000000123 anti-resoprtive effect Effects 0.000 claims abstract 6
- 230000000694 effects Effects 0.000 claims abstract 5
- 210000000963 osteoblast Anatomy 0.000 claims abstract 5
- 230000003190 augmentative effect Effects 0.000 claims abstract 2
- 230000015572 biosynthetic process Effects 0.000 claims abstract 2
- 230000001939 inductive effect Effects 0.000 claims abstract 2
- 102000003982 Parathyroid hormone Human genes 0.000 claims 18
- 108090000445 Parathyroid hormone Proteins 0.000 claims 18
- 239000000199 parathyroid hormone Substances 0.000 claims 18
- 229960001319 parathyroid hormone Drugs 0.000 claims 18
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 claims 8
- 229960003773 calcitonin (salmon synthetic) Drugs 0.000 claims 6
- 108010068072 salmon calcitonin Proteins 0.000 claims 6
- 108090000932 Calcitonin Gene-Related Peptide Proteins 0.000 claims 4
- 102000004414 Calcitonin Gene-Related Peptide Human genes 0.000 claims 4
- 239000002639 bone cement Substances 0.000 claims 4
- 102000055006 Calcitonin Human genes 0.000 claims 3
- 108060001064 Calcitonin Proteins 0.000 claims 3
- 102100021926 Low-density lipoprotein receptor-related protein 5 Human genes 0.000 claims 3
- 238000002347 injection Methods 0.000 claims 3
- 239000007924 injection Substances 0.000 claims 3
- 102000018233 Fibroblast Growth Factor Human genes 0.000 claims 2
- 108050007372 Fibroblast Growth Factor Proteins 0.000 claims 2
- 102000038461 Growth Hormone-Releasing Hormone Human genes 0.000 claims 2
- 239000000095 Growth Hormone-Releasing Hormone Substances 0.000 claims 2
- 102000003745 Hepatocyte Growth Factor Human genes 0.000 claims 2
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 claims 2
- 101001043594 Homo sapiens Low-density lipoprotein receptor-related protein 5 Proteins 0.000 claims 2
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 claims 2
- 108700020797 Parathyroid Hormone-Related Proteins 0.000 claims 2
- 102000043299 Parathyroid hormone-related Human genes 0.000 claims 2
- 102000019307 Sclerostin Human genes 0.000 claims 2
- 108050006698 Sclerostin Proteins 0.000 claims 2
- 101710142969 Somatoliberin Proteins 0.000 claims 2
- 102000013275 Somatomedins Human genes 0.000 claims 2
- 108010009583 Transforming Growth Factors Proteins 0.000 claims 2
- 102000009618 Transforming Growth Factors Human genes 0.000 claims 2
- 239000012190 activator Substances 0.000 claims 2
- 210000001185 bone marrow Anatomy 0.000 claims 2
- 229960004015 calcitonin Drugs 0.000 claims 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 claims 2
- 229940126864 fibroblast growth factor Drugs 0.000 claims 2
- 229940088597 hormone Drugs 0.000 claims 2
- 239000005556 hormone Substances 0.000 claims 2
- 230000000921 morphogenic effect Effects 0.000 claims 2
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 claims 2
- 108090000623 proteins and genes Proteins 0.000 claims 2
- 102000004169 proteins and genes Human genes 0.000 claims 2
- OGBMKVWORPGQRR-UMXFMPSGSA-N teriparatide Chemical group C([C@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](N)CO)C(C)C)[C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CNC=N1 OGBMKVWORPGQRR-UMXFMPSGSA-N 0.000 claims 2
- VUBUAHHUDGCHIN-LPJXTDOQSA-N (2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-aminopropanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-4-carboxybutanoyl]amino]-3-methylpentanoyl]amino]-5-oxopentanoyl]amino]-3-phenylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-oxobutanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]hexanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-4-carboxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-4-carboxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-methylpentanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]-5-oxopentanoyl]amino]butanedioic acid Chemical compound CC[C@H](C)[C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](C)N)C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O VUBUAHHUDGCHIN-LPJXTDOQSA-N 0.000 claims 1
- 229940122361 Bisphosphonate Drugs 0.000 claims 1
- KSIYPKPZIBBUFR-LJNLPFSOSA-N CSCC[C@H](NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1)C(C)C)C(=O)NCC(=O)N[C@@H](Cc1ccccc1)C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(N)=O Chemical compound CSCC[C@H](NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1)C(C)C)C(=O)NCC(=O)N[C@@H](Cc1ccccc1)C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(N)=O KSIYPKPZIBBUFR-LJNLPFSOSA-N 0.000 claims 1
- 208000000094 Chronic Pain Diseases 0.000 claims 1
- 102000008186 Collagen Human genes 0.000 claims 1
- 108010035532 Collagen Proteins 0.000 claims 1
- 102000009123 Fibrin Human genes 0.000 claims 1
- 108010073385 Fibrin Proteins 0.000 claims 1
- 102000008946 Fibrinogen Human genes 0.000 claims 1
- 108010049003 Fibrinogen Proteins 0.000 claims 1
- 101000741447 Gallus gallus Calcitonin Proteins 0.000 claims 1
- 102000018997 Growth Hormone Human genes 0.000 claims 1
- 108010051696 Growth Hormone Proteins 0.000 claims 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims 1
- 101000741445 Homo sapiens Calcitonin Proteins 0.000 claims 1
- 102000016267 Leptin Human genes 0.000 claims 1
- 108010092277 Leptin Proteins 0.000 claims 1
- 108010015167 Low Density Lipoprotein Receptor-Related Protein-5 Proteins 0.000 claims 1
- 208000002193 Pain Diseases 0.000 claims 1
- 229930003316 Vitamin D Natural products 0.000 claims 1
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 230000004075 alteration Effects 0.000 claims 1
- 230000001195 anabolic effect Effects 0.000 claims 1
- 150000004663 bisphosphonates Chemical group 0.000 claims 1
- 210000000459 calcaneus Anatomy 0.000 claims 1
- 230000001126 calcilytic effect Effects 0.000 claims 1
- 239000001506 calcium phosphate Substances 0.000 claims 1
- 229910000389 calcium phosphate Inorganic materials 0.000 claims 1
- 235000011010 calcium phosphates Nutrition 0.000 claims 1
- 239000001175 calcium sulphate Substances 0.000 claims 1
- 235000011132 calcium sulphate Nutrition 0.000 claims 1
- XFWJKVMFIVXPKK-UHFFFAOYSA-N calcium;oxido(oxo)alumane Chemical compound [Ca+2].[O-][Al]=O.[O-][Al]=O XFWJKVMFIVXPKK-UHFFFAOYSA-N 0.000 claims 1
- 229920001436 collagen Polymers 0.000 claims 1
- 239000000512 collagen gel Substances 0.000 claims 1
- 239000004053 dental implant Substances 0.000 claims 1
- 230000001076 estrogenic effect Effects 0.000 claims 1
- 229940012952 fibrinogen Drugs 0.000 claims 1
- 239000000122 growth hormone Substances 0.000 claims 1
- 229940045644 human calcitonin Drugs 0.000 claims 1
- 210000002758 humerus Anatomy 0.000 claims 1
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 claims 1
- 229940039781 leptin Drugs 0.000 claims 1
- NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 claims 1
- 230000011164 ossification Effects 0.000 claims 1
- 229920000642 polymer Polymers 0.000 claims 1
- 150000003180 prostaglandins Chemical class 0.000 claims 1
- 230000000541 pulsatile effect Effects 0.000 claims 1
- 230000011664 signaling Effects 0.000 claims 1
- 238000005728 strengthening Methods 0.000 claims 1
- 229910052712 strontium Inorganic materials 0.000 claims 1
- CIOAGBVUUVVLOB-UHFFFAOYSA-N strontium atom Chemical compound [Sr] CIOAGBVUUVVLOB-UHFFFAOYSA-N 0.000 claims 1
- 239000000725 suspension Substances 0.000 claims 1
- 230000008685 targeting Effects 0.000 claims 1
- 210000002303 tibia Anatomy 0.000 claims 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims 1
- 235000019166 vitamin D Nutrition 0.000 claims 1
- 239000011710 vitamin D Substances 0.000 claims 1
- 150000003710 vitamin D derivatives Chemical class 0.000 claims 1
- 229940046008 vitamin d Drugs 0.000 claims 1
- JDJALSWDQPEHEJ-LMVCGNDWSA-N x4853 Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 JDJALSWDQPEHEJ-LMVCGNDWSA-N 0.000 claims 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/29—Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Physical Education & Sports Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Epidemiology (AREA)
- Endocrinology (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Materials For Medical Uses (AREA)
- Dental Preparations (AREA)
- Surgical Instruments (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
A method for augmenting bone in a subject in need thereof including installing within an interior portion of a bone located in the subject a sufficient amount of a biocompatible material to form a scaffold within the bone interior, wherein the scaffold serves as a support for the formation of new bone within the bone interior portion, and administering to the subject a sufficient amount of at least one bone augmentation agent to elevate blood concentration of at least one anabolic agent in the subject. The method may further include administering at least one anti-resorptive agent to the subject in an amount sufficient to substantially prevent resorption of new bone growth. In another embodiment, the method may further include a step of mechanically inducing an increase in osteoblast activity in the subject, wherein the elevation in blood concentration of the anabolic agent and the increase in osteoblast activity at least partially overlap in time.
Claims (31)
1. A method for augmenting bone in a subject in need thereof, said method comprising:
(a) mechanically inducing an increase in osteoblast activity within said subject;
(b) installing within an interior portion of a bone within said subject where the increase in osteoblast activity has been induced a sufficient amount of a biocompatible material to form a scaffold within said bone interior, said scaffold serving as a support for formation of new bone within said interior portion ; and (c) administering to said subject a sufficient amount of at least one bone augmentation agent to elevate blood concentration of at least one bone anabolic agent in said subject, wherein the elevation in blood concentration of the anabolic agent in said subject and the increase in osteoblast activity therein at least partially overlap in time.
(a) mechanically inducing an increase in osteoblast activity within said subject;
(b) installing within an interior portion of a bone within said subject where the increase in osteoblast activity has been induced a sufficient amount of a biocompatible material to form a scaffold within said bone interior, said scaffold serving as a support for formation of new bone within said interior portion ; and (c) administering to said subject a sufficient amount of at least one bone augmentation agent to elevate blood concentration of at least one bone anabolic agent in said subject, wherein the elevation in blood concentration of the anabolic agent in said subject and the increase in osteoblast activity therein at least partially overlap in time.
2. The method according to claim 1, wherein the biocompatible material is selected from the group consisting of biologically active bone cements, bone morphogenic proteins, polymers, fibrinogen, synthetic fibrins, collagen gels, collagen with hydroxyapatite suspensions and combinations thereof.
3. The method according to claim 2, wherein the biocompatible material is a biologically active bone cement and the bone cement is selected from the group consisting of calcium phosphate, calcium hydroxyapatite, calcium sulphate and calcium aluminate.
4. The method according to claim 1, wherein the bone augmentation agent is a bone anabolic agent.
5. The method according to claim 4, wherein the bone anabolic agent is selected from the group consisting of a parathyroid hormone (PTH), anabolic Vitamin D analogs, a low-density lipoprotein receptor-related protein 5(LRP5) activator, or an inhibitor of sclerostin binding to LRP5, an activator of non-genomic estrogen-like signaling (ANGELS), a bone morphogenic protein (BMP), an insulin-like growth factor (IGF), a fibroblast growth factor (FGF), leptin, a prostaglandin, a statin, strontium, a growth hormone, a growth hormone releasing factor (GHRF), hepatocyte growth factor (HGF), calcitonin gene related peptide (CGRP), parathyroid hormone related peptide (PTHrP), transforming growth factor (TGF)-.beta.1 and combinations thereof.
6. The method according to claim 5, wherein the bone anabolic agent is a parathyroid hormone and said hormone is selected from the group consisting of a natural parathyroid hormone, a truncate of natural parathyroid hormone, an amidated truncate of natural parathyroid hormone, an amidated natural parathyroid hormone and combinations thereof.
7. The method according to claim 6, wherein a sufficient amount of said parathyroid hormone is administered to said subject to achieve a pulsatile blood concentration thereof in said subject of between about 50-350 pg/ml.
8. The method according to claim 6, wherein said sufficient amount of parathyroid hormone is from about 10 µg -10mg pure weight of PTH hormone per dose.
9. The method according to claim 6, wherein said parathyroid hormone is administered via injection and the sufficient amount of parathyroid hormone is from about
10-200 µg per dose.
10. The method according to claim 6, wherein the bone anabolic agent is PTH[1-34] in the free acid form.
10. The method according to claim 6, wherein the bone anabolic agent is PTH[1-34] in the free acid form.
11. The method according to claim 6, wherein the bone anabolic agent is an amidated truncate of natural parathyroid hormone and said truncate is selected from the group consisting of PTH[1-30]NH2, PTH[1-31]NH2, PTH[1-32]NH2, PTH[1-33]NH2, PTH[1-34]NH2 and combinations thereof.
12. The method according to claim 1, wherein the bone augmentation agent is at least one agent that causes elevated levels of an endogenous anabolic agent within said subject.
13. The method according to claim 12, wherein the agent causing an increased expression of the endogenous bone anabolic agent within said subject is selected from the group consisting of calcilytic agents and antibodies to sclerostin.
14. The method according to claim 1, which further comprises administering to the subject an anti-resorption agent, said anti-resorptive agent being administered in an amount sufficient to substantially prevent resorption of said new bone growth.
15. The method according to claim 14, wherein the anti-resorptive agent is a bisphosphonate or a calcitonin selected from the group consisting of human calcitonin, salmon calcitonin, eel calcitonin, elkatonin, porcine calcitonin, chicken calcitonin, calcitonin gene related peptide (CGRP) and combinations thereof.
16. The method according to claim 15, wherein the antiresorptive agent is salmon calcitonin and wherein the salmon calcitonin is administered to said subject in an amount calculated to achieve a substantially continuous blood concentration thereof of between about 5-500 pg/ml.
17. The method according to claim 16, wherein the amount of salmon calcitonin is from about µg to 5 mg pure weight of the calcitonin per dose.
18. The method according to claim 16, wherein the salmon calcitonin is administered via injection and the amount of salmon calcitonin is from about 5 µg - 200 µg per dose.
19. The method according to claim 1 wherein the bone augmentation agent is a parathyroid hormone and wherein blood concentration of the parathyroid hormone in said subject is raised to a level of between about 50-350 pg/ml by no later than 7 days following said mechanical inducement.
20. The method according to claim 1, additionally comprising forming a sufficient amount of additional bone in a jaw region of said subject to provide an anchor for a dental implant implanted into said jaw region.
21. The method according to claim 1, additionally comprising forming a sufficient amount of additional bone in one or more targeted bones of said subject to permit a prosthetic device implanted into at least one said targeted bone to be securely anchored thereto.
22. The method according to claim 1, additionally comprising forming a sufficient amount of additional bone in said subject to serve as a secure anchor for a hollow, adjustable insert anchored to said additional bone.
23. The method according to claim 1, which further comprises targeting at least one vertebra of said subject for additional bone formation and wherein a sufficient amount of bone is added to said at least one vertebra such that the subject is substantially freed from chronic pain caused due to vertebral crush.
24. The method according to claim 1, wherein additional bone is formed on at least one vertebra of said subject in an amount sufficient to stabilize said at least one vertebra due to strengthening thereof.
25. The method according to claim 1, wherein the biocompatible material is administered via an injection into a location selected from the group consisting of the proximal femoral, the hip, the distal radius, the proximal humerus, the calcaneus, the ribs, the tibia and the sacrum.
26. The method according to claim 1, wherein the bone augmentation agent is administered in a manner selected from the group consisting of orally, nasally, trans-dermally, rectally, subcutaneously and intravenously.
27. A kit for fostering and preserving bone growth in an interior portion of a bone lacking a sufficient trabecular scaffolding to substantially prevent resorption of new bone formed therein, said kit comprising:
(a) at least one container having therein at least one biocompatible material adapted for forming an additional amount of scaffolding within said bone interior portion;
(b) at least one container having therein a bone augmentation agent; and (c) a mechanical alteration device for altering contents of a bone marrow cavity in at least one targeted bone.
(a) at least one container having therein at least one biocompatible material adapted for forming an additional amount of scaffolding within said bone interior portion;
(b) at least one container having therein a bone augmentation agent; and (c) a mechanical alteration device for altering contents of a bone marrow cavity in at least one targeted bone.
28. The kit according to claim 27, wherein the biocompatible material is a biologically active bone cement.
29. The kit according to claim 27, wherein the bone augmentation agent is a bone anabolic agent.
30. The kit according to claim 27, further comprising at least one container having therein at least one anti-resorptive agent.
31. The kit according to claim 27, further comprising an evacuation device for evacuating at least a portion of the contents of said bone marrow cavity.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US2007/010267 WO2008133618A1 (en) | 2007-04-27 | 2007-04-27 | Methods and compositions for fostering and preserving bone growth |
Publications (1)
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|---|---|
| CA2685407A1 true CA2685407A1 (en) | 2008-11-06 |
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Family Applications (1)
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|---|---|---|---|
| CA002685407A Abandoned CA2685407A1 (en) | 2007-04-27 | 2007-04-27 | Methods and compositions for fostering and preserving bone growth |
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| JP (1) | JP2010526064A (en) |
| CN (1) | CN101663043B (en) |
| AU (1) | AU2007352435B2 (en) |
| CA (1) | CA2685407A1 (en) |
| WO (1) | WO2008133618A1 (en) |
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| CN101966348B (en) * | 2010-09-21 | 2014-03-26 | 中国科学院深圳先进技术研究院 | Strontium-doped hydroxyapatite and collagen composite material and application and preparation method thereof |
| TWI573558B (en) * | 2015-09-30 | 2017-03-11 | 愛派司生技股份有限公司 | Bone plate set having screws with a plurality of threaded areas |
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| ES2262642T3 (en) * | 2000-04-05 | 2006-12-01 | Kyphon Inc. | DEVICE FOR THE TREATMENT OF FRACTURED AND / OR SICK BONES. |
| AU1331302A (en) * | 2000-10-16 | 2002-04-29 | Univ South Carolina Res Found | Biocompatible cement containing reactive calcium phosphate nanoparticles and methods for making and using such cement |
| WO2002080933A1 (en) * | 2001-04-03 | 2002-10-17 | The Royal Alexandra Hospital For Children | A drug for use in bone grafting |
| CN1294885C (en) * | 2001-06-05 | 2007-01-17 | 江苏阳生生物工程有限公司 | Biotechnological body bone tissue rack and its making process and use |
| TWI267378B (en) * | 2001-06-08 | 2006-12-01 | Wyeth Corp | Calcium phosphate delivery vehicles for osteoinductive proteins |
| JP2005508217A (en) * | 2001-09-21 | 2005-03-31 | ストライカー コーポレイション | Pore former for orthopedic cement |
| CN1622826A (en) * | 2002-01-17 | 2005-06-01 | 德克萨斯系统大学董事会 | Stimulation of bone growth and cartilage formation with thrombing peptide derivatives |
| SE0300620D0 (en) * | 2003-03-05 | 2003-03-05 | Bone Support Ab | A new bone substitute composition |
| US9532994B2 (en) * | 2003-08-29 | 2017-01-03 | The Regents Of The University Of California | Agents and methods for enhancing bone formation by oxysterols in combination with bone morphogenic proteins |
| US7531518B2 (en) * | 2004-05-14 | 2009-05-12 | Unigene Laboratories Inc. | Method for fostering bone formation and preservation |
| US7175858B2 (en) * | 2004-07-26 | 2007-02-13 | Skeletal Kinetics Llc | Calcium phosphate cements and methods for using the same |
| US20060089723A1 (en) * | 2004-10-25 | 2006-04-27 | Murphy Kieran P | Method for bone augmentation |
| KR20070108170A (en) * | 2005-01-06 | 2007-11-08 | 쿠로스 바이오서저리 아게 | Supplemented matrices for the repair of bone fractures |
| JP2006263184A (en) * | 2005-03-24 | 2006-10-05 | Gc Corp | Bone cement injection and filling method and leakage prevention bag for injecting and filling bone cement |
| CN101217972B (en) * | 2005-05-11 | 2013-05-29 | 尤尼基因实验室公司 | Method for fostering bone formation and preservation |
| US20060293667A1 (en) * | 2005-05-19 | 2006-12-28 | Agnes Vignery | Bone implant device and methods of using same |
| US7691105B2 (en) * | 2005-09-26 | 2010-04-06 | Depuy Spine, Inc. | Tissue augmentation, stabilization and regeneration technique |
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| WO2008133618A1 (en) | 2008-11-06 |
| AU2007352435A1 (en) | 2008-11-06 |
| CN101663043B (en) | 2014-03-12 |
| CN101663043A (en) | 2010-03-03 |
| AU2007352435B2 (en) | 2012-01-19 |
| EP2139507A4 (en) | 2012-06-06 |
| JP2010526064A (en) | 2010-07-29 |
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