Researchers are studying treatment of osteoporotic fractures. Subjects with pelvic fractures due to osteoporosis are divided into 2 groups. The control group receives physical therapy along with calcium and vitamin D supplementation. The experimental group receives a parathyroid hormone analogue in addition to the standard therapy. It is found that the subjects who receive hormonal treatment have a shorter time to fracture healing and improved functional outcome. The benefits of the investigational medication are attributed to increased osteoblastic activity. An elevated level of which of the following markers is most likely to reflect the medication effect in these subjects?

Question

Researchers are studying treatment of osteoporotic fractures.  Subjects with pelvic fractures due to osteoporosis are divided into 2 groups.  The control group receives physical therapy along with calcium and vitamin D supplementation.  The experimental group receives a parathyroid hormone analogue in addition to the standard therapy.  It is found that the subjects who receive hormonal treatment have a shorter time to fracture healing and improved functional outcome.  The benefits of the investigational medication are attributed to increased osteoblastic activity.  An elevated level of which of the following markers is most likely to reflect the medication effect in these subjects?

Quizplus · Accepted Answer

11ec160b_3d00_b34c_9249_3b34b2a4317c_MD0001_00 Bone is continually broken down and reformed by the process known as bone remodeling, which consists of the coordinated activity of osteoblasts (responsible for bone formation) and osteoclasts (responsible for bone resorption). The subjects in this study are receiving a recombinant parathyroid hormone analog (eg, teriparatide), which promotes bone formation by stimulating maturation of pre-osteoblasts into osteoblasts. Osteoblasts synthesize bone matrix and express alkaline phosphatase (AlkP), which promotes normal bone mineralization by increasing local concentrations of inorganic phosphorus. Serum AlkP levels correlate with osteoblastic activity. However, total serum levels are nonspecific, as AlkP is also produced by the hepatobiliary tree, intestine, and placenta and may be elevated due to other causes (eg, pregnancy, biliary obstruction). If the source of AlkP is uncertain, AlkP isoenzymes (ie, liver, placental, intestinal, bone) can be differentiated with additional laboratory techniques (eg, electrophoresis, immunoassay). Other markers of osteoblast activity include N-terminal propeptide of type 1 procollagen (PINP), which is released during post-translation cleavage of type 1 procollagen before its assembly into mature type 1 collagen fibrils. (Choice B) Aspartate aminotransferase (AST) is predominantly found in liver, muscle, and kidneys. AST is commonly used as a marker for hepatic injury and is also elevated in rhabdomyolysis and myocardial infarction. (Choice C) Calcitonin is secreted by the parafollicular C cells of the thyroid and inhibits bone resorption by osteoclasts. As a laboratory marker, calcitonin is primarily used in the diagnosis of medullary thyroid cancer; it does not mark osteoblastic activity. (Choice D) Acid phosphatase is a family of lysosomal enzymes present in a wide variety of cells, including osteoclasts (the acid phosphatase in osteoclasts is resistant to degradation by tartrate). However, osteoblasts do not express acid phosphatase. (Choices E and F) Osteoclastic activity (ie, bone resorption) leads to breakdown of fibrillar collagen with release of biomarkers such as hydroxyproline and collagen telopeptides. Increased urine levels are associated with states of increased bone resorption (rather than formation). Educational objective: Bone-specific alkaline phosphatase levels correlate with osteoblast activity. Other markers of osteoblast activity include N-terminal propeptide of type 1 procollagen, which is released during post-translation cleavage of type 1 procollagen. __________ References: International Osteoporosis Foundation and International Federation of Clinical Chemistry and Laboratory Medicine position on bone marker standards in osteoporosis. (http://www.ncbi.nlm.nih.gov/pubmed/21605012) Teriparatide increases the maturation of circulating osteoblast precursors. (http://www.ncbi.nlm.nih.gov/pubmed/21617993)

Researchers Are Studying Treatment of Osteoporotic Fractures