Tag Archives: abstract

Teriparatide Increases Bone Strength More Than Density

Abstract

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

Teriparatide Decreases Bone Density, but Not Strength

Abstract

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.

Macdonald HM, Nishiyama KK, Hanley DA, Boyd SK
Osteoporos Int Jan 2011
PMID: 20458576 | Full Text

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 [6] 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 [20]. This was likely due to localization of the porosity near the endocortical surface where its influence on bone’s mechanical properties is minimal [20], 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 [19] and monkeys [20] 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 [18]. 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 [24], 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.

Teriparatide Stimulates Bone Formation and Resorption, and Decreases Fracture Risk

Abstract

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.

Neer RM, Arnaud CD, Zanchetta JR, Prince R…
N. Engl. J. Med. May 2001
PMID: 11346808 | Free Full Text

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

Orange Improves Bone in Orchidectomized Rats

Abstract

Feeding orange pulp improved bone quality in a rat model of male osteoporosis.

Oxidative stress and inflammation have been linked to bone loss. We evaluated the effects of feeding orange pulp (OP), a source of vitamin C and flavonoids, on bone quality in a rat model of male osteoporosis. One-year-old retired breeder rats (n = 43) were orchidectomized (ORX) or sham-operated (SHAM). Three days postsurgery, ORX rats were randomly assigned to treatments: ORX or ORX with 2.5% OP, 5% OP, or 10% OP. Diets were isonitrogenous, isocaloric, modified AIN-93M diets with equal fiber content. All ORX rats were fed for 4 months to the mean food intake of the SHAM group. At the end of the study blood, urine and bone samples were collected. Plasma antioxidant capacity and urinary deoxypyridinoline (DPD) were determined. Bone density, structure, and strength were assessed using dual energy X-ray absorptiometry, microcomputed tomography, and finite element analyses. ORX decreased (P < .05) antioxidant status, while OP as low as 2.5% maintained the antioxidant capacity of ORX rats comparable to that of the SHAM group. Cortical thickness at the tibial midshaft was significantly decreased by ORX and increased by OP, and urinary DPD was significantly increased by ORX and decreased by OP. In fourth lumbar trabecular cores, ORX rats had significantly reduced bone volume fraction, connectivity density, and trabecular number and increased trabecular separation. OP significantly increased bone volume fraction and trabecular number and decreased trabecular separation in ORX rats. Improvements due to OP in microarchitectural properties of vertebral bones and in cortical thickness of long bones were subtle but significant. The consistently negative impacts of ORX on bone density, structure, and strength parameters confirm the previously reported importance of testosterone for bone.

Morrow R, Deyhim F, Patil BS, Stoecker BJ
J Med Food Apr 2009
PMID: 19459729

Fruit + Vegetables Fails to Improve Bone Over 16 Weeks

Abstract

Effect of increased fruit and vegetable consumption on bone turnover in older adults: a randomised controlled trial.

Evidence suggests that increased fruit and vegetable (FV) intake may be associated with improved bone health, but there is limited evidence from intervention trials to support this. This 16-week study showed that increased FV consumption (five or more portions per day) does not have any effect on the markers of bone health in older adults.
Observational evidence suggests that increased FV consumption may be associated with improved bone health. However, there is lack of evidence from intervention trials to support this. This study examined the effect of increased FV consumption on bone markers among healthy, free-living older adults.
A randomised controlled trial was undertaken. Eighty-three participants aged 65-85 years, habitually consuming less than or equal to two portions of FV per day, were randomised to continue their normal diet or to consume five or more portions of FV per day for 16 weeks. FV were delivered to all participants each week, free of charge. Compliance was assessed at baseline and at 6, 12 and 16 weeks by diet histories and biomarkers of micronutrient status. Fasting serum bone markers (osteocalcin (OC) and C-terminal telopeptide of type 1 collagen (CTX)) were measured using enzyme-linked immunosorbent assay.
Eighty-two participants completed the intervention. The five portions per day group showed a significantly greater change in daily FV consumption compared to the two portions per day group (p < 0.001), and this was reflected in significant increases in micronutrient status. No significant differences were evident in change in bone markers between the two portions per day group and the five portions per day group over the 16 weeks (geometric mean of week 16 to baseline ratio (95% confidence interval): OC-0.95 (0.89-1.02) and 1.04 (0.91-1.18), respectively, p = 0.25; CTX-1.06 (0.95-1.19) and 0.98 (0.90-1.06) respectively, p = 0.20).
Increased FV consumption had no effect on bone markers in older adults. Larger intervention studies of longer duration are warranted to establish whether long-term FV consumption can benefit bone health.

Neville CE, Young IS, Gilchrist SE, McKinley MC…
Osteoporos Int Jan 2014
PMID: 23716039

Grapefruit Improves Bone Quality in Orchidectomized Rats Again

Abstract

Grapefruit juice modulates bone quality in rats.

Hypogonadism and oxidative stress increase the risk for developing osteoporosis. The objective of this research was to evaluate the efficacy of drinking grapefruit juice on bone quality in orchidectomized (ORX) and non-ORX rats. Fifty-six 90-day-old male Sprague-Dawley rats were equally divided into four groups–non-ORX rats (sham), sham + grapefruit juice, ORX, and ORX + grapefruit juice–and treated for 60 days. Thereafter, all rats were sacrificed to determine the plasma antioxidant status, insulin-like growth factor I (IGF-I), and indices of bone turnover, bone quality, and calcium and magnesium concentrations in the bone, urine, and feces. Orchidectomy decreased (P < .05) antioxidant status, bone quality, and bone mineral contents and increased (P < .05) indices of bone turnover, urinary deoxypridinoline, calcium, and magnesium, and fecal calcium excretions. In contrast to the ORX group, ORX rats that drank grapefruit juice had an increase (P < .05) in antioxidant status, bone density, and bone mineral contents, delayed femoral fracture, and slowed down (P < .05) bone turnover rate and tended to have a decrease (P = .08) in urinary deoxypridinoline. In sham-treated animals, drinking grapefruit juice increased (P < .05) bone density and tended to increase the femoral strength. The concentration of IGF-I in the plasma was not affected across treatments. In conclusion, drinking grapefruit juice positively affected bone quality by enhancing bone mineral deposition in ORX rats and by improving bone density in non-ORX rats via an undefined mechanism.

Deyhim F, Mandadi K, Faraji B, Patil BS
J Med Food Mar 2008
PMID: 18361744

Grapefruit Improves Bone Quality in Orchidectomized Rats

Abstract

Grapefruit pulp increases antioxidant status and improves bone quality in orchidectomized rats.

Orchidectomy causes oxidative stress and increases the incidence of osteoporosis. The objective of this research was to evaluate whether eating grapefruit pulp (GP) modifies antioxidant status and reduces osteoporosis in orchidectomized rats.
Fifty-six 90-d-old male Sprague-Dawley rats were randomized into two groups: sham-control group (n = 14) and orchidectomized (ORX) group (n = 42). The orchidectomized group was equally divided among the following three treatments: orchidectomy, orchidectomy + 5.0% GP, and orchidectomy + 10% GP. At the termination of the study (day 60), all rats were euthanized and the plasma was collected for antioxidant status and indices of bone turnover. Bone quality and mineral contents in the bone, urine, and feces were evaluated.
Orchidectomy lowered (P < 0.05) antioxidant status, bone quality, bone mineral contents and elevated (P < 0.05) indices of bone turnover, urinary deoxypyridinoline, and fecal calcium excretion. In contrast to the ORX group, independent of dosage, antioxidant status, bone density, and delayed time-induced femoral fracture were higher (P < 0.05) in the GP groups, whereas fecal calcium excretion and urinary deoxypyridinoline excretion were lowered (P < 0.05). GP dose-dependently slowed down bone turnover (P < 0.05), elevated bone calcium and magnesium contents (P < 0.05), tended to lower urinary excretion of magnesium, and numerically improved bone strength.
The beneficial effects of eating red grapefruit on bone quality of ORX rats is due to bone mineral deposition and slowed-down bone turnover.

Deyhim F, Mandadi K, Patil BS, Faraji B
Nutrition Oct 2008
PMID: 18595661

Citrus Positively Affects Bone Strength in Rats

Abstract

Citrus juice modulates bone strength in male senescent rat model of osteoporosis.

An experiment evaluated the effect of citrus juice on enhancing serum antioxidant status and on osteoporosis prevention in orchidectomized rats.
Thirty-six 1-y-old male rats were randomized to two groups: a sham-control group (n = 9) and an orchidectomized group (n = 27). The orchidectomized group was divided into three groups of nine and assigned to one of the following treatments: orchidectomy, orchidectomy plus orange juice, and orchidectomy plus grapefruit juice. Sixty days after initiation of the study, all rats were killed, blood was collected, and serum was harvested for total antioxidant status and indices of bone formation and resorption. Femoral density and biomechanical properties were monitored.
Orchidectomy decreased (P < 0.05) total antioxidant capacity, femoral density, and biomechanical properties and increased (P < 0.05) alkaline phosphatase, acid phosphatase, and urinary excretion of hydroxyproline compared with the sham-control group. In contrast to orchidectomy, orchidectomy plus orange juice and orchidectomy plus grapefruit juice reversed (P < 0.05) orchidectomy-induced antioxidant suppression, decreased (P < 0.05) alkaline phosphatase and acid phosphatase activities, moderately restored (P = 0.07) femoral density, increased (P < 0.05) femoral strength, significantly delayed time-induced femoral fracture, and decreased (P < 0.05) urinary excretion of hydroxyproline.
The present study supports the supposition in that drinking citrus juice positively affects serum antioxidant status and bone strength.

Deyhim F, Garica K, Lopez E, Gonzalez J…
Nutrition May 2006
PMID: 16472977

Cranberry Inhibits Osteoclasts In Vitro

Abstract

A-type cranberry proanthocyanidins inhibit the RANKL-dependent differentiation and function of human osteoclasts.

This study investigated the effect of A-type cranberry proanthocyanidins (AC-PACs) on osteoclast formation and bone resorption activity. The differentiation of human pre-osteoclastic cells was assessed by tartrate-resistant acid phosphatase (TRAP) staining, while the secretion of interleukin-8 (IL-8) and matrix metalloproteinases (MMPs) was measured by ELISA. Bone resorption activity was investigated by using a human bone plate coupled with an immunoassay that detected the release of collagen helical peptides. AC-PACs up to 100 µg/mL were atoxic for osteoclastic cells. TRAP staining evidenced a dose-dependent inhibition of osteoclastogenesis. More specifically, AC-PACs at 50 µg/mL caused a 95% inhibition of RANKL-dependent osteoclast differentiation. This concentration of AC-PACs also significantly increased the secretion of IL-8 (6-fold) and inhibited the secretion of both MMP-2 and MMP-9. Lastly, AC-PACs (10, 25, 50 and 100 µg/ml) affected bone degradation mediated by mature osteoclasts by significantly decreasing the release of collagen helical peptides. This study suggests that AC-PACs can interfere with osteoclastic cell maturation and physiology as well as prevent bone resorption. These compounds may be considered as therapeutic agents for the prevention and treatment of periodontitis.

Tanabe S, Santos J, La VD, Howell AB…
Molecules 2011
PMID: 21399573 | Free Full Text

Cranberry Juice No Effect on Bone Quality in Rats

Abstract

Cranberry juice improved antioxidant status without affecting bone quality in orchidectomized male rats.

We reported that drinking citrus juice improves bone quality in orchidectomized senescent male rats. Because cranberry juice, like citrus, is rich in nutrients and phenolic compounds, beneficial effects of citrus juice might also be seen with cranberry juice. An experiment evaluated effect of drinking cranberry juice on bone quality in orchidectomized rats.
Thirty-two 1-year-old male rats were randomized to two groups: a sham-control group (n=8) and an orchidectomized group (n=24). The treatments for the 4 months duration of the study were SHAM, orchidectomy (ORX), ORX+drinking either 27% or 45% cranberry juice concentrate added to drinking water. At the termination of the study, the rats were euthanized, blood was collected for plasma antioxidant status and IGF-I. The femur, tibia and the 4th lumbar were evaluated for bone quality. Total calcium and magnesium concentration in the femurs were also evaluated.
ORX did not affect red blood cell (RBC)-induced hemolysis despite lowering (p<0.05) plasma antioxidant capacity; reduced (p<0.05) plasma IGF-I, femoral density, femoral strength, time-induced femoral fracture, bone mineral content, bone mineral area; numerically (p=0.07) lowered 4th lumbar density; decreased (p<0.05) trabecular connectivity, trabecular number, femoral ash; increased (p<0.05) trabecular separation in comparison to the SHAM group. Drinking cranberry juice increased (p<0.05) plasma antioxidant status, protected RBC against hemolysis, but had no positive effect on bone quality or bone mineral status.
Cranberry juice increases plasma antioxidant status without affecting bone quality.

Villarreal A, Stoecker BJ, Garcia C, Garcia K…
Phytomedicine Dec 2007
PMID: 17481874