Abstract
Bisphosphonates are well known inhibitors of osteoclast activity and thus may be employed to influence osteoblast activity. The present study was designed to evaluate the in vivo effects of zoledronic acid (ZA) on the proliferation and osteoblastic commitment of mesenchymal stem cells (MSC) in osteoporotic patients. We studied 22 postmenopausal osteoporotic patients. Densitometric, biochemical, cellular and molecular data were collected before as well as after 6 and 12 months of ZA treatment. Peripheral blood MSC-like cells were quantified by colony-forming unit fibroblastic assay; their osteogenic differentiation potential was evaluated after 3 and 7 days of induction, respectively. Circulating MSCs showed significantly increased expression levels of osteoblastic marker genes such as Runt-related transcription factor 2 (RUNX2), and Osteonectin (SPARC) during the 12 months of monitoring time. Lumbar bone mineral density (BMD) variation and SPARC gene expression correlated positively. Bone turnover marker levels were significantly lowered after ZA treatment; the effect was more pronounced for C terminal telopeptide (CTX) than for Procollagen Type 1 N-Terminal Propeptide (P1NP) and bone alkaline phosphatase (bALP). Our findings suggest a discrete anabolic activity supported by osteogenic commitment of MSCs, consequent to ZA treatment. We confirm its anabolic effects in vivo on osteogenic precursors.
Highlights
Osteoporosis is a degenerative disease associated with bone fractures affecting mobility and increasing mortality and morbidity in older populations [1]
Bone turnover marker levels were significantly lowered after zoledronic acid (ZA) treatment; the effect was more pronounced for C terminal telopeptide (CTX) than for Procollagen Type 1 N-Terminal Propeptide (P1NP) and bone alkaline phosphatase
Histomorphometric analyses revealed adipocytic replacement in the bone marrow of postmenopausal osteoporotic patients [5]; we have demonstrated in a previous study that mesenchymal stem cells of osteoporotic patients have an abnormal osteogenic differentiation [6]
Summary
Osteoporosis is a degenerative disease associated with bone fractures affecting mobility and increasing mortality and morbidity in older populations [1]. Bone resorption is associated with osteoclastic activity, and increases in postmenopausal osteoporosis leading to an imbalance in bone homeostasis. The bone loss observed with aging is associated with the increased activity of osteoclasts, and with a progressive decline in osteoblast number, function, and survival that is concurrent to the generation of bone formation impairment [2]. The ability to produce an adequate number of functional osteoblasts is pivotal for bone mass preservation. With regard to this aspect, it has been demonstrated that bone remodeling involves the proliferation and osteogenic differentiation of mesenchymal stem cells [3]. Mesenchymal stem cells (MSC) can differentiate into adipocytes; a mutually inhibitory relationship exists between osteogenic and adipogenic lineage commitment [4]
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