Clinical Usefulness of Urinary Hydroxyproline as a Biochemical Marker of Bone Resorption

Ondokuı Mayıs Üniversitesi Dişhekimliği Fakültesi Dergisi: 2002; 3(1): 17-19 17 Clinical Usefulness o f Urinary Hydroxyproline as a Biochemical Marker o f Bone Resorption Üriner Hidroksiprolinin Kemik Rezorbsiyonu Biyokimyasal Belirleyicisi Olarak Klinik Yararlılığı Barış ŞİMŞEK*, Doç.Dr. Özgül KARACAER**, Prof.Dr. İnci KARACA* ÖZET: Hidroksiprolin kollajen yıkımının ürünü olan modifiye amino asiddir. Tip I kollajen osteoblastlann majör ürünüdür. K em ik resorpsiyoııu sırasında, hidroksiprolin serbest veya kol lajen molekülüne yapışmış fragm anlar olarak salınabilir. K ol lajen sentezinde yeniden kullanılmazlar. Hidroksiprolin konıplemeııt ve iskelet olmayan kollajeniıı yıkımında da serbestleşir. Üre hidroksiprolini kem ik resorpsiyonunda marker olarak se nelerdir kullanılmaktadır. Ancak, salgılanmadan önce yüksek oranda metaboUze olur ve hidroksiprolinin üriner salgısı total kollajen kataboliznıin sadece % 10 unu temsil eder. Üriner hid roksiprolin kemik resorpsiyonunun çoğunlukla kullanılan markerıdır ancak duyarlılık ve spesifiteye gereksinim duyulur. Eğer sınırlar uygun olarak ilişkilendirilirse hidroksiprolin ölçümleri metabolik aktivitenin tayin edilmesinde uygunluk sağlar. Anahtar kelimeler: Kemik resorpsiyoııu, kemik resorpsiyon nıarkerları, üriner hidroksiprolin SUIVliViARY: Hydroxyproline is a m odified amino acid that is metabolic product o f collagen breakdown. Type I collagen is a m ajor product o f osteoblast. D uring bone resorption, hydroxyproline may be released either free or with fragm ents o f the collagen molecule attached. It is not reutilized in collagen synthesis. Hydroxyproline is also liberated by the breakdown o f complement and nonskeletal collagen. Urine hydroxyproline as a marker o f bone resorption has long been in use fo r years. H o wever, it is highly m etabolized before being excreted and uri nary excretion o f hydroxyproline represents only about 10 % o f total collagen catabolism. Urinary hydroxyproline is the com monly used marker o f bone resorption, but it lacks sensitivity and specificity. I f the limitations can be dealth with appropri ately, hydroxyproline measurements can provide a reasonable means o f assessing metabolic activity. Key words: Bone resorption, bone resorption marker; urinary hydroxyproline Bone metabolism is characterized by a dynamic and con tinuous process to maintain a balance between the resorption of old and injured bone initiated by osteo clasts, and the formation of new bone under the control of osteoblasts. This continuous degradation and forma tion of bone throughout life is termed bone remodelling or bone turnover. The balance between bone resorption and bone formation, which is altered in most metabolic diseases is important in the maintenance of normal bone turnover1^*. The state of the skeleton can be assessed by a wide vari ety of procedures, including histomorphometry and mea surement of calcium fluxes. Histomorphometry is inva sive, expensive, has a long turnaround time, and is limit ed to a single skeletal site, iliac crest. Measurement of calcium fluxes is technically difficult5. In recent years, additional techniques for assessing the skeleton, includ ing improved radiological and densitométrie procedures and newer computer-assisted imaging methods for bone, * Department of OraI and Maxillofacial Surgery, Faculty o f Dentistry, University o f Gazi ** Department of Prosthodontics, Faculty o f Dentistry, University of Gazi have been developed. However, these methods are also expensive and inconvenient and cannot be performed at sufficiently frequent intervals to reveal dynamic changes in the skeleton6-8. This void has been filled with the identification of biochemical markers of bone remodel ing, the monitoring of which is noninvasive, inexpen sive, and can be repeated often5. Most of the new bio chemical markers have been targeted for use in assessing bone resorption since bone loss due to metabolic bone disease is the more important clinical factor to monitor and evaluate in bone disease9’10. Biochemical markers of bone resorption that reflect osteoclast activity and/or col lagen degradation provide a new and potentially impor tant clinical tool for the assessment and monitoring of bone metabolism1’11. Metabolic products of bone colla gen breakdown have been the recent focus of laboratory methods designed to assess bone resorption12. Urine hydroxyproline as a marker of collagen breakdown has been in use for years1’6’9’12. Hydroxyproline is a modified amino acid that is derived from proline by a posttranslation hydroxylation occuring within the peptid chain. Hydroxyproline is found mainly in collagens, comprising about 13% of the amino acid content of these proteins1’13’14. Because free hydroxypro line liberated from the breakdown of collagen is not 18 reutilized for collagen biosynthesis, most of the endoge nous hydroxyproline present in biological fluids is derived from the degradation of various forms of colla gen14'15. About 90% of the hydroxyproline released by the breakdown of collagen in the tissues, especially dur ing bone resorption is degraded to free amino acid form that readily passes through the glomerulus. It is eventu ally completely oxidized and catabolized in the liver to urea and carbon dioxide16-17. The remaining 10% of the hydroxyproline is released in small polypeptide chains that pass through the glomerulus and are excreted in urine without any further metabolism1'3-5. Since half of human collagen resides in bone, excretion of hydroxyproline in urine is regarded as a marker of bone resoption3-4-14. The major component of bone matrix is Type I collagen, which is rich in hydroxypro line6'18. Although some Type I collagen is present in nonskeletal tissues, bone has a much higher proportion and a much higher turnover5. Approximately 50% of uri nary hydroxyproline is derived from bone collagen breakdown5-19. Although hydroxyproline constitutes a substantial pro portion of the amino acid content of Type I bone colla gen and measurement of this amino acid has been used to monitor bone resorption1, the urinary total hydrox yproline represents only a small fraction of total collagen catabolism, and this method is not very specific to Type I bone collagen6-13'14’20. There are a number of issues that can lead to a lack of tissue specificity1. Hydroxyproline is also liberated by the breakdown of complement5. The C 1q fraction of complement contains a structural region that is similar to collagen, containing significant amounts of hydroxyproline and could account for up to 40% of urinary hydroxyproline16'21. For this reason inflammatory conditions can cause dra matic increases in urine excretion of hydroxyproline1'22. Hydroxyproline is also found in nonskeletal collagen sources including Type II collagen of cartilage and skin12. It is also released by the breakdown of procolla gen I extension peptides5-19. Hydroxyproline from pro collagen I aminoterminal propeptide (PI (...truncated)