# US 5,700,694 A · Method to detect bone and other connective tissue disorders in humans and animals > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 5,700,694 A - Document ID: US5700694A - Status: Granted - Kind: A - Application number: 08/485,823 - Filed: 1995-06-06 - Granted: 1997-12-23 - Earliest claimed: 1989-12-30 - Assignees: Rowett Research Institute - Inventors: Simon Peter Robins - Web page: https://patentgrep.com/patent/US5700694A ## CPC - C07K 16/18: against material from animals or humans - C07K 16/44: against material not provided for elsewhere {, e.g. haptens, metals, DNA, RNA, amino acids} - G01N 33/6887: {from muscle, cartilage or connective tissue} - G01N 2800/108: Osteoporosis - Y10S 436/811: Test for named disease, body condition or organ function - Y10S 436/813: Cancer - Y10S 436/815: Test for named compound or class of compounds - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS ## Abstract The invention is directed to methods to assess connective tissue, especially bone, metabolism in disease or to monitor therapy, which method comprises assessing the levels of native free collagen-derived crosslinks in biological fluids, especially urine. The method can be enhanced by concomitantly determining the levels of an indicator of bone formation in biological fluids of the same individual and assessing the differences between the degradation marker and the formation indicator. Antibodies which are specifically immunoreactive with forms of crosslinks which occur free in biological fluids are also disclosed. ## Claims ### Claim 1 A method to monitor or diagnose the presence of a disorder associated with a connective tissue metabolism abnormality, which method comprises comparing the level of native free crosslinks derived from collagen in a non-hydrolyzed biological fluid of a human subject with the level of said crosslinks in normal subjects so as to diagnose a subject having an enhanced level of said crosslinks as showing the presence of said disorder, wherein said crosslinks are selected from native peptide free non-glycosylated pyridinoline (N-Pyd), native peptide-free deoxypyridinoline (N-Dpd), or the sum of N-Pyd and N-Dpd. ### Claim 2 (depends on 1) The method of claim 1 which further includes determining the level of an indicator of bone formation in said biological fluid, determining the difference between the level of said selected native free crosslinks and the level of said indicator, and comparing this difference with the corresponding difference in normal subjects so as to monitor or diagnose a subject having an increase in said difference as showing the presence of said disorder. ### Claim 3 (depends on 1) The method of claim 1 wherein said biological fluid is serum or urine. ### Claim 4 (depends on 2) The method of claim 2 wherein said biological fluid is serum or urine. ### Claim 5 (depends on 1) The method of claim 1 wherein said free crosslinks are determined as the sum of N-Pyd and N-Dpd. ### Claim 6 (depends on 2) The method of claim 2 wherein said free crosslinks are determined as the sum of N-Pyd and N-Dpd. ### Claim 7 (depends on 1) The method of claim 1 wherein said free crosslinks are determined as N-Dpd. ### Claim 8 (depends on 2) The method of claim 2 wherein said free crosslinks are determined as N-Dpd. ### Claim 9 (depends on 1) The method of claim 1 wherein said free crosslinks are determined as N-Pyd. ### Claim 10 (depends on 2) The method of claim 2 wherein said free crosslinks are determined as N-Pyd. ### Claim 11 (depends on 1) The method of claim 1, wherein said disorder is related to osteoporosis, hyperparathyroidism, rheumatoid arthritis, osteoarthritis, a malignant tumor or metastatic cancer in bone, or Paget's disease. ### Claim 12 (depends on 1) The method of claim 1, wherein the bone resorption disorder relates to osteoporosis. ### Claim 13 (depends on 1) The method of claim 1, wherein the bone resorption disorder relates to hyperparathyroidism. ### Claim 14 (depends on 1) The method of claim 1, wherein the bone resorption disorder relates to rheumatoid arthritis. ### Claim 15 (depends on 1) The method of claim 1, wherein the bone resorption disorder relates to osteoarthritis. ### Claim 16 (depends on 1) The method of claim 1, wherein the bone resorption disorder relates to a malignant tumor or metastatic cancer in bone. ### Claim 17 (depends on 1) The method of claim 1, wherein the bone resorption disorder relates to Paget's disease. ### Claim 18 (depends on 1) The method of claim 1, wherein said biological fluid is urine. ### Claim 19 (depends on 1) The method of claim 1, wherein said biological fluid is serum. ### Claim 20 (depends on 19) The method of claim 19, wherein said crosslinks are N-Pyd. ### Claim 21 (depends on 19) The method of claim 19, wherein said crosslinks are N-Dpd. ### Claim 22 (depends on 19) The method of claim 19, wherein said crosslinks are the sum of N-Pyd and N-Dpd. ### Claim 23 (depends on 19) The method of claim 19, wherein said disorder is related to osteoporosis, hyperparathyroidism, rheumatoid arthritis, osteoarthritis, a malignant tumor or metastatic cancer in bone, or Paget's disease. ### Claim 24 (depends on 23) The method of claim 23, wherein said crosslinks are N-Pyd. ### Claim 25 (depends on 23) The method of claim 23, wherein said crosslinks are N-Dpd. ### Claim 26 (depends on 23) The method of claim 23, wherein said crosslinks are the sum of N-Pyd and N-Dpd.