New developments in the treatment of osteoporosis.
The last 25 years have seen the development of a plethora of new, effective agents for the treatment of osteoporosis. These agents reduce the risk of spine fractures by up to 70%, hip fractures by 40-50% and non-vertebral fractures by up to 50-80%. Amino-bisphosphonates, taken orally or intravenously, remain the dominant treatment modalities for osteoporosis. These so-called anti-resorptive or anti-catabolic agents stabilize the skeleton and reduce fracture risk in osteoporotic as well as osteopenic individuals. A monoclonal antibody against receptor activator of nuclear factor κB ligand, Denosumab, constitutes a new anti-resorptive agent recently approved worldwide. In younger postmenopausal women, low-dose estrogen or estrogen/progestin still has a place for short-term (up to 5 years) preservation of bone mass, especially in women with menopausal symptoms. Likewise, selective estrogen receptor modulators should be considered in younger postmenopausal women, especially those at increased risk of breast cancer. Anabolic (bone forming) regimens, of which parathyroid hormone is the only agent currently available, aid in the build up of new bone, increase bone mass and improve bone architecture. In cancellous bone, 30-60% increases of bone mass have been documented, but cortical bone thickness also increases. These improvements lead to profound reduction in fracture rates in both the axial and appendicular skeleton. Owing to cost and the need for parenteral administration, in most countries these agents are reserved for severe osteoporosis with multiple fractures.
Femoral strength in osteoporotic women treated with teriparatide or alendronate.
To gain insight into the clinical effect of teriparatide and alendronate on the hip, we performed non-linear finite element analysis of quantitative computed tomography (QCT) scans from 48 women who had participated in a randomized, double-blind clinical trial comparing the effects of 18-month treatment of teriparatide 20 μg/d or alendronate 10mg/d. The QCT scans, obtained at baseline, 6, and 18 months, were analyzed for volumetric bone mineral density (BMD) of trabecular bone, the peripheral bone (defined as all the cortical bone plus any endosteal trabecular bone within 3 mm of the periosteal surface), and the integral bone (both trabecular and peripheral), and for overall femoral strength in response to a simulated sideways fall. At 18 months, we found in the women treated with teriparatide that trabecular volumetric BMD increased versus baseline (+4.6%, p<0.001), peripheral volumetric BMD decreased (-1.1%, p<0.05), integral volumetric BMD (+1.0%, p=0.38) and femoral strength (+5.4%, p=0.06) did not change significantly, but the ratio of strength to integral volumetric BMD ratio increased (+4.0%, p=0.04). An increase in the ratio of strength to integral volumetric BMD indicates that overall femoral strength, compared to baseline, increased more than did integral density. For the women treated with alendronate, there were small (<1.0%) but non-significant changes compared to baseline in all these parameters. The only significant between-treatment difference was in the change in trabecular volumetric BMD (p<0.005); related, we also found that, for a given change in peripheral volumetric BMD, femoral strength increased more for teriparatide than for alendronate (p=0.02). We conclude that, despite different compartmental volumetric BMD responses for these two treatments, we could not detect any overall difference in change in femoral strength between the two treatments, although femoral strength increased more than integral volumetric BMD after treatment with teriparatide.
Keaveny TM, McClung MR, Wan X, Kopperdahl DL…
Bone Jan 2012 PMID: 22015818
Changes in trabecular and cortical bone microarchitecture at peripheral sites associated with 18 months of teriparatide therapy in postmenopausal women with osteoporosis.
We used high-resolution peripheral quantitative computed tomography (HR-pQCT) to monitor changes in bone microarchitecture and strength at the distal radius and tibia associated with 18 months of teriparatide therapy in postmenopausal women with osteoporosis. Despite treatment-associated declines in total and cortical BMD, trabecular thinning and reduced trabecular bone volume, bone strength did not change significantly from baseline.
Teriparatide is an established anabolic therapy for osteoporosis; however, treatment effects at the distal radius are unclear. Therefore, we aimed to monitor changes in bone microarchitecture and estimated strength at the distal radius and tibia in osteoporotic postmenopausal women.
We used high-resolution peripheral quantitative computed tomography (Scanco Medical, Switzerland) to perform a standard three-dimensional morphological analysis of the distal radius and tibia in 11 osteoporotic postmenopausal women (mean age, 68.7 ± 12.7 years) at baseline, 6, 12, and 18 months after initiation of 20 μg/day of teriparatide. Ten of the women received bisphosphonate therapy prior to starting on teriparatide. In addition to the standard analysis, we quantified cortical bone mineral density (BMD), porosity, and thickness using an automated segmentation procedure and estimated bone strength (ultimate stress) using finite element analysis. After 18 months, we observed a decrease in total BMD (p = 0.03) at the distal radius and a decrease in cortical BMD at the distal radius (p = 0.05) and tibia (p = 0.01). The declines in cortical BMD were associated with trends for increased cortical porosity at both sites. At the distal radius, 18 months of teriparatide treatment was also associated with trabecular thinning (p = 0.009) and reduced trabecular bone volume ratio (p = 0.08). We observed similar trends at the distal tibia. Despite these changes in bone quality, bone strength was maintained over the 18-month follow-up.
The observed changes in cortical bone structure are consistent with the effects of parathyroid hormone on intracortical bone remodeling. Controlled trials involving larger sample sizes are required to confirm the effects of teriparatide therapy on trabecular and cortical microarchitecture in the peripheral skeleton.
Although our sample size was small, our results are consistent with previous reports of declines in cortical BMD at the radius [8, 9, 18] and at the femoral neck  with teriparatide therapy. The decrease in cortical BMD in the present study was coupled with increased cortical porosity at both sites; however, cortical porosity was only statistically different from baseline at the distal tibia after 12 months. Despite a more porous cortex, FE analysis indicated that bone strength did not appear to be compro- mised with teriparatide treatment. This finding supports observations from animal models in which treatment with PTH activated intracortical remodeling and lead to in- creased intracortical porosity [19, 20], but did not compro- mise bone strength . This was likely due to localization of the porosity near the endocortical surface where its influence on bone’s mechanical properties is minimal , although this spatial distribution needs to be confirmed in future HR-pQCT studies. In the present study, a slightly thicker cortical shell and enlarged cortical area may also have offset the higher cortical porosity at the distal tibia. Similar changes in cortical bone geometry were observed in rabbits  and monkeys  treated with PTH and were attributed to increased bone formation on the endocortical surface. In addition, postmenopausal women treated with teriparatide for a median of 18 months had significantly larger cortical area at the distal radius compared with untreated women as measured with pQCT, but no pretreatment com- parison was obtained . Whether PTH has an anabolic effect on the periosteal surface remains unclear [19, 20]….
We acknowledge limitations of our study including the small sample size and the fact that all but one of the women had received prior therapy with bisphosphonates. The degree to which prior bisphosphonate therapy blunts the bone response to teriparatide remains unclear, as in some instances, it does not appear to do so [4, 23]. Since distal radius fractures are recognized indicators of osteoporosis , there is an obvious need for larger clinical trials that employ HR-pQCT to monitor and compare the treatment- related effects of teriparatide on bone microarchitecture and strength in treatment-naïve subjects and subjects with a history of bisphosphonate therapy.
Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis.
Once-daily injections of parathyroid hormone or its amino-terminal fragments increase bone formation and bone mass without causing hypercalcemia, but their effects on fractures are unknown.
We randomly assigned 1637 postmenopausal women with prior vertebral fractures to receive 20 or 40 microg of parathyroid hormone (1-34) or placebo, administered subcutaneously by the women daily. We obtained vertebral radiographs at base line and at the end of the study (median duration of observation, 21 months) and performed serial measurements of bone mass by dual-energy x-ray absorptiometry.
New vertebral fractures occurred in 14 percent of the women in the placebo group and in 5 percent and 4 percent, respectively, of the women in the 20-microg and 40-microg parathyroid hormone groups; the respective relative risks of fracture in the 20-microg and 40-microg groups, as compared with the placebo group, were 0.35 and 0.31 (95 percent confidence intervals, 0.22 to 0.55 and 0.19 to 0.50). New nonvertebral fragility fractures occurred in 6 percent of the women in the placebo group and in 3 percent of those in each parathyroid hormone group (relative risk, 0.47 and 0.46, respectively [95 percent confidence intervals, 0.25 to 0.88 and 0.25 to 0.861). As compared with placebo, the 20-microg and 40-microg doses of parathyroid hormone increased bone mineral density by 9 and 13 more percentage points in the lumbar spine and by 3 and 6 more percentage points in the femoral neck; the 40-microg dose decreased bone mineral density at the shaft of the radius by 2 more percentage points. Both doses increased total-body bone mineral by 2 to 4 more percentage points than did placebo. Parathyroid hormone had only minor side effects (occasional nausea and headache).
Treatment of postmenopausal osteoporosis with parathyroid hormone (1-34) decreases the risk of vertebral and nonvertebral fractures; increases vertebral, femoral, and total-body bone mineral density; and is well tolerated. The 40-microg dose increased bone mineral density more than the 20-microg dose but had similar effects on the risk of fracture and was more likely to have side effects.
Parathyroid hormone stimulates bone formation and resorption and can increase or decrease bone mass, depending on the mode of administration. Continuous infusions and daily subcutaneous injections of parathyroid hormone stimulate bone formation similarly but have different effects on bone resorption and bone mass.1,2 Continuous infusions, which result in a persistent elevation of the serum parathyroid hormone concentration, lead to greater bone resorption than do daily injections, which cause only transient increases in the serum parathyroid hormone concentration.3
One thing that bothers me about her talk is that she claims Teriparatide is the only thing in the world that builds bone by increasing osteoblast activity. I’ve posted many studies that found increases in osteoblasts from a variety of things. She also didn’t mention any other potentially helpful dietary supplements besides Calcium and Vitamin D. Like most MDs, she is probably unaware of anything that is not FDA approved.