Bisphosphonate-osteoclasts: changes in osteoclast morphology and function induced by antiresorptive nitrogen-containing bisphosphonate treatment in osteoporosis patients

TY - JOUR

T1 - Bisphosphonate-osteoclasts: changes in osteoclast morphology and function induced by antiresorptive nitrogen-containing bisphosphonate treatment in osteoporosis patients

AU - Jobke, Björn

AU - Milovanovic, Petar

AU - Amling, Michael

AU - Busse, Björn

N1 - Björn Jobke als interne Person anlegen

PY - 2014/2/1

Y1 - 2014/2/1

N2 - Osteoclasts are unique cells capable of bone resorption and therefore have become a major target in osteoporosis treatment strategies. Bisphosphonates suppress bone turnover via interference with the internal enzymatic cell system of osteoclasts leading to cytoskeletal disruption. This mechanism found its clinical relevance in reducing bone resorption, stabilizing bone mass and reducing fracture risk in osteoporosis patients. However, knowledge about specific in vivo changes in osteoclast cell morphology and function is still insufficient. We examined osteoclasts in 23 paired bone biopsies from osteoporosis patients (18 males, 5 females; age: 52.6±11.5yrs) under nitrogen-containing bisphosphonate administration with a mean treatment duration of three years. Formalin-fixed, undecalcified sections were assessed by qualitative and quantitative bone histomorphometry, where the osteoclast morphology, nuclei, distribution, location as well as resorption parameters were investigated to obtain information about cell function and viability. After three years of treatment, resorption parameters decreased significantly while the number of osteoclasts remained unchanged. Out of 23 patients, nine developed previously termed "giant-osteoclasts" with increased size, numerous nuclei (>10 nuclei/Oc) and oftentimes detachment from the bone surface. These cells frequently had pycnotic nuclei and other morphological signs suggestive of osteoclast apoptosis. Characteristic large-sized osteoclasts were uniquely found in patients treated with nitrogen-containing bisphosphonates, thus being clearly distinguishable from giant-osteoclasts in other bone disorders such as Paget disease, secondary hyperparathyroidism or osteopetrosis. The resorption indices of large-sized osteoclasts, specifically the eroded perimeter and erosion depth, revealed significantly reduced values but not an entirely inhibited resorption capability. Bisphosphonate-osteoclasts' viability and affinity to bone seem significantly disturbed while the apoptotic process may be prolonged for a yet unknown period of time in favor of maintaining a low bone turnover.

AB - Osteoclasts are unique cells capable of bone resorption and therefore have become a major target in osteoporosis treatment strategies. Bisphosphonates suppress bone turnover via interference with the internal enzymatic cell system of osteoclasts leading to cytoskeletal disruption. This mechanism found its clinical relevance in reducing bone resorption, stabilizing bone mass and reducing fracture risk in osteoporosis patients. However, knowledge about specific in vivo changes in osteoclast cell morphology and function is still insufficient. We examined osteoclasts in 23 paired bone biopsies from osteoporosis patients (18 males, 5 females; age: 52.6±11.5yrs) under nitrogen-containing bisphosphonate administration with a mean treatment duration of three years. Formalin-fixed, undecalcified sections were assessed by qualitative and quantitative bone histomorphometry, where the osteoclast morphology, nuclei, distribution, location as well as resorption parameters were investigated to obtain information about cell function and viability. After three years of treatment, resorption parameters decreased significantly while the number of osteoclasts remained unchanged. Out of 23 patients, nine developed previously termed "giant-osteoclasts" with increased size, numerous nuclei (>10 nuclei/Oc) and oftentimes detachment from the bone surface. These cells frequently had pycnotic nuclei and other morphological signs suggestive of osteoclast apoptosis. Characteristic large-sized osteoclasts were uniquely found in patients treated with nitrogen-containing bisphosphonates, thus being clearly distinguishable from giant-osteoclasts in other bone disorders such as Paget disease, secondary hyperparathyroidism or osteopetrosis. The resorption indices of large-sized osteoclasts, specifically the eroded perimeter and erosion depth, revealed significantly reduced values but not an entirely inhibited resorption capability. Bisphosphonate-osteoclasts' viability and affinity to bone seem significantly disturbed while the apoptotic process may be prolonged for a yet unknown period of time in favor of maintaining a low bone turnover.

U2 - 10.1016/j.bone.2013.10.024

DO - 10.1016/j.bone.2013.10.024

M3 - SCORING: Journal article

C2 - 24211427

VL - 59

SP - 37

EP - 43

JO - BONE

JF - BONE

SN - 8756-3282

ER -