Overview, Vol 10, Issue 2


Lewiecki et al report that once-monthly oral ibandronate administered for 12 months increased integral total hip QCT BMD and DXA areal BMD. FEA-derived hip strength to density ratio and femoral, peripheral, and trabecular strength increased with ibandronate while improved vertebral, peripheral, and trabecular strength and anteroposterior bending stiffness vs. placebo improved. HSA-estimated femoral neck outer diameter increased, the latter is probably an artefact given the drug is not an anabolic agent. J Clin Endocrinol Metab 2009;94:171-80


Grey et al make an important contribution to therapeutics by demonstrating that the beneficial effects of zoledronic acid may persist during two years. In 50 postmenopausal women with osteopenia, zoledronate decreased markers of bone turnover for 2 years. Between-groups differences in markers of bone turnover and bone mineral density were similar at 12 and 24 months. Mild secondary hyperparathyroidism was present throughout the study in the zoledronate group. J Clin Endocrinol Metab 2009;94:538-44

PTH – stimulating the phagocytes, or does it?

Jilka et al confront the challenging issue of why PTH cannot seem to stimulate periosteal apposition, at least in human subjects. The investigators make the point that the anabolic action on the endosteal surface thrives on the ability to inhibit apoptosis of the many osteoblasts cells produced by high remodeling. The periosteum is a pretty quiet place after completion of growth and so PTH does not have many cells to inhibit the apoptosis of. Instead it must exert pro-differentiating and/or pro-survival effects on postmitotic preosteoblasts. Bone 2009;44:275-86

Recker et al report 100 µg PTH(1-84) given for 18 (n=8) or 24 (n=7) months and 8 placebo treated subjects. Cancellous bone volume was 45-48% higher due to higher trabecular number (Tb.N) and produced by intratrabecular tunneling. Trabecular thickness and connectivity density was higher. Cancellous bone formation rate was 2-fold higher because of greater mineralizing surface. Osteoclast and eroded surface were unaffected and there were no effects on cortical thickness, or endocortical, or periosteal BFR; porosity tended to be higher. Bone 2009;44:113-9


Silverman et al report that in a 3-year, randomized, double-blind, placebo-controlled study, 6847 women with osteoporosis (55-85 years of age) received bazedoxifene 20 or 40 mg/d, raloxifene 60 mg/d, or placebo. New vertebral fractures were lower with bazedoxifene 20 mg (2.3%), bazedoxifene 40 mg (2.5%), and raloxifene 60 mg (2.3%) than placebo (4.1%); relative risk reductions of 42%, 37%, and 42%, respectively. In a post hoc analysis of women at higher fracture risk, bazedoxifene 20 mg showed a 50% and 44% reduction in nonvertebral fractures relative to placebo (p=0.02) and raloxifene 60 mg (p=0.05), respectively. J Bone Miner Res 2008;23:1923-34



Epidemiology in Taiwan

Shao et al report that 75,482 hip fractures occurred during 7 years with an incidence rate of 57.54 per 10,000 per year but increasing by 30% during 7 years and more greatly in males (36%) than in females (22%). The average female-to-male ratio was 1.76, lower than those in many countries. In females, cervical fracture was higher than that of trochanteric fractures, while the incidence of trochanteric fractures was higher than cervical fractures in males (p<0.0001). Bone 2009;44:125-9


Asaba et al report that activation of the renin-angiotensin system activation induces high turnover osteoporosis with accelerated bone resorption. Angiotensin II (AngII) acted on osteoblasts and increased RANKL and vascular endothelial growth factor stimulating formation of osteoclasts. Knockdown of AT2 receptor inhibited the AngII activity, whereas silencing of the AT1 receptor enhanced it. ACE inhibitor, enalapril, improved osteoporosis; whereas losartan exacerbated the low bone mass phenotype. J Bone Miner Res 2009;24:241-50

Successful skeletal aging

Cauley et al present an interesting study suggesting there is a group of women who lose little or no bone with advancing age. If this is the case, then the pathogenetic mechanisms identifying those who lose little bone and those who lose a great deal of bone need to be studied. Out of 8224 subjects measured over 15 years, about 10% lost little or no BMD. These subjects had a 20% lower risk of nonspine fracture and 67% lower risk of hip fracture. Mortality risks were also lower. J Bone Miner Res 2009;24:134-43

Coupling factor?

Walker et al report that cardiotrophin (CT-1) signals through gp130 and the LIF receptor is expressed in osteoclasts and increases osteoblast activity and mineralization in vitro and in vivo. In neonate CT-1(-/-) mice, low bone mass associated with reduced osteoblasts and many large osteoclasts, but increased cartilage remnants within the bone suggest impaired resorption. Cultured marrow from CT-1(-/-) mice generated osteoclasts and mineralized poorly. As the CT-1(-/-) mice aged, the reduced osteoblast surface (ObS/BS) was no longer detected, but impaired bone resorption continued resulting in an osteopetrotic phenotype. CT-1 is an osteoclast-derived stimulus of bone formation and resorption. J Bone Miner Res 2008;23:2025-32

CatK knockout

Pennypacker et al report that CatK null mice have osteopetrosis. CatK (-/-) mice had less lamellar cortical bone. Higher bone volume, trabecular thickness, and trabecular number were observed at the distal femur with a smaller marrow cavity a sign of decreased endocortical resorption. Bone 2009;44:199-207

Note from the Editor

The purpose of Progress in Osteoporosis is to provide the reader with a summary of the most important literature published in the preceding three to four months in the field of osteoporosis. Most reviews and original research are cited. In addition, summaries and figures are provided for readers who may not have easy access to all the specialist literature. The summaries are based on the contents of abstracts, which have been abbreviated to concisely convey the main theme. The contents of the abstracts and figures should be used only as a means of directing the reader to the original literature and should not be quoted verbatim or cited as a reference. The opinions expressed in the Overview are my own and do not necessarily reflect those of the International Osteoporosis Foundation.