The new frontier of bone formation: a breakthrough in postmenopausal osteoporosis?
OBJECTIVE
Osteoporosis is a chronic disease that accelerates after menopause in many women. Most of the pharmacologic attempts to control the disease, such as hormone therapy, have emphasized the constraint of bone resorption. Since recent years have witnessed important advances in the field of bone formation, this review aims to update the present knowledge on the mechanisms affecting osteoblastogenesis and on the therapeutic results achieved by recently approved drugs.


METHODS
We sought peer-reviewed, full-length basic and clinical articles published between 1995 and May 2008 using a PubMed search strategy, with the terms osteoporosis and osteoblast, osteoporosis and strontium ranelate, and osteoporosis and parathyroid hormone (PTH). This search was further supplemented by a hand-search of reference lists of selected review papers. After crossing-cleaning the reference lists, some 800 articles were selected. Articles on regulators of osteoblast differentiation and function, together with well-designed clinical studies, were surveyed.


RESULTS
A complex network of systemic and local factors regulates osteoblastogenesis. Advances in fracture protection have been published in clinical studies with PTH. Some investigators claim an anabolic effect for strontium ranelate, which also confers protection against fracture.


CONCLUSIONS
The control of bone formation offers new clinical potential. Stimulation of bone formation by PTH has translated into fracture protection. The action of strontium ranelate has been claimed to be mediated by some level of bone formation, but this hypothesis still needs clarification.
Department of Obstetrics and Gynecology, Hospital Clínico Universitario, Valencia, Spain.
C
C
Ruiz
N
N
Abril
J J
JJ
Tarín
M A
MA
García-Pérez
A
A
Cano
D000368:Aged; D000818:Animals; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D005260:Female; D050723:Fractures, Bone / Q000517:prevention & control; D005786:Gene Expression Regulation; D006801:Humans; D008875:Middle Aged; D009942:Organometallic Compounds / Q000627:therapeutic use; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D010281:Parathyroid Hormone / Q000627:therapeutic use; D013876:Thiophenes / Q000627:therapeutic use
D050071:Bone Density Conservation Agents; D009942:Organometallic Compounds; D010281:Parathyroid Hormone; D013876:Thiophenes; C081587:strontium ranelate