Category Archives: Alendronate

Low-Dose Alendronate Effect is Similar to Standard-Dose in Chinese Women with Bone Loss


Effect of low-dose alendronate treatment on bone mineral density and bone turnover markers in Chinese postmenopausal women with osteopenia and osteoporosis.

The aim of this study was to evaluate the effect of low-dose alendronate (ALN) treatment on bone mineral density (BMD) and bone turnover markers in Chinese postmenopausal women with osteopenia and osteoporosis.
This study was a large-sample, randomized, open-label, prospective, multicenter, clinical trial with a 12-month follow-up. A total of 639 postmenopausal women (aged 62.2 ± 7.0 y) with osteopenia or osteoporosis were randomized into two groups: low-dose ALN (70 mg every two weeks) and standard-dose ALN (70 mg weekly). All patients were also supplemented with calcium (600 mg) and vitamin D3 (125 IU) daily. BMD (measured by dual-energy x-ray absorptiometry; Hologic and Lunar) and levels of serum bone turnover markers (bone resorption marker, carboxy-telopeptide of type I collagen; bone formation marker, alkaline phosphatase) were assessed at baseline and at 3, 6, and 12 months of treatment. BMD and bone turnover markers were compared between the baseline and the end of treatment, and the changes in BMD and bone turnover markers were also compared between the low-dose ALN group and the standard-dose ALN group.
No significant differences in age, years since menopause, body mass index, BMD, 25-hydroxy vitamin D level, and serum biochemical markers were found at baseline between the two dose groups. A total of 558 (87.3%) and 540 (84.5%) women completed the treatment at the 6th and 12th months, respectively. After the 12-month treatment, lumbar spine and hip BMD increased and serum bone turnover markers decreased significantly in both of the treatment groups (P < 0.01), and no differences in percentage changes in BMD at the lumbar spine, femoral neck, and hip were found between the low-dose group (5.60%, 3.87%, and 3.28%, respectively) and the standard-dose group (5.07%, 2.93%, and 3.80%, respectively; P > 0.05). However, levels of serum alkaline phosphatase and carboxy-telopeptide of type I collagen in the standard-dose group decreased moderately compared with those in the low-dose group (P < 0.05 and P < 0.01). The women tolerated the two doses of ALN quite well. Adverse effects were similar in the two groups.
Treatment with low-dose ALN (70 mg every two weeks) in women with postmenopausal osteopenia or osteoporosis effectively increases lumbar spine and hip BMD, similar to treatment with standard-dose ALN. Low-dose ALN may be a cost-effective and safe protocol for treating osteopenia or osteoporosis in Chinese women.

Li M, Zhang ZL, Liao EY, Chen DC…
Menopause Jan 2013
PMID: 22968256

Teriparatide Increases Bone Strength More Than Density


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

Eldecalcitol > Alfacalcidol in Ovariectomized Rats


Effects of combined treatment with eldecalcitol and alendronate on bone mass, mechanical properties, and bone histomorphometry in ovariectomized rats: a comparison with alfacalcidol and alendronate.

Eldecalcitol (ELD), a 2β-hydroxypropyloxy derivative of 1α,25 (OH) 2D3, inhibits bone resorption more potently than alfacalcidol (ALF) while maintaining osteoblastic function in an ovariectomized (OVX) osteoporosis rat model. Alendronate (ALN), which is the most common bisphosphonate used for the treatment of osteoporosis, increases the bone mineral density (BMD) by suppressing bone resorption. In this study, we investigated the effects of combination treatments with ELD and ALN or with ALF and ALN on bone mass and strength in OVX rats. Seventy female rats, 32 weeks old, were assigned to seven groups: (1) a sham-operated control group; (2) an OVX-control group; (3) an ELD group; (4) an ALF group; (5) an ALN group; (6) an ELD+ALN group; and (7) an ALF+ALN group. OVX rats were orally treated with ELD (0.015 μg/kg), ALF (0.0375 μg/kg), or ALN (0.2mg/kg) daily for 12 weeks. In both the lumbar spine and the femur, ELD and ALF monotherapy significantly increased the BMD, and ELD+ALN and ALF+ALN significantly increased the BMD, compared with ALN monotherapy, as an additive effect. In particular, ELD+ALN resulted in a significantly higher BMD than ALF+ALN in the femur. On mechanical testing of the lumbar spine, ELD and ALF monotherapy significantly increased the ultimate load, and ELD+ALN and ALF+ALN significantly increased the ultimate load compared with ALN monotherapy. In the femur, ELD, ELD+ALN, and ALF+ALN treatment significantly increased the ultimate load, compared with the OVX-control group, and ELD+ALN resulted in a significantly higher ultimate load than ALN monotherapy. A histomorphometric analysis showed that ELD monotherapy and ELD+ALN combination therapy had a potent inhibitory effect on bone resorption parameters (osteoclast surface and eroded surface), while maintaining bone formation parameters (osteoblast surface and osteoid surface). By contrast, ALF and ALF+ALN significantly lowered the histological parameters of both bone resorption and formation. These results suggested that ELD or ALF used in combination with ALN has therapeutic advantages over ALN monotherapy, with ELD+ALN combination treatment producing an especially beneficial anti-osteoporotic effect by inhibiting osteoclastic bone resorption and maintaining osteoblastic function, compared with ALF+ALN combination treatment.

Sugimoto M, Futaki N, Harada M, Kaku S
Bone Jan 2013
PMID: 23041510

Video: Dr. Hofflich “Osteoporosis Update 2013” – Stein Institute for Research on Aging

Here is a nice talk by Dr. Heather Hofflich from May 15, 2013. She’s an Associate Professor of Medicine at UCSD. She gives an overview of osteoporosis and discusses the causes and therapies used to treat it. She also takes a look at recent controversies in treatment plans and vitamin usage.

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.

Alendronate Suppresses Bone Formation From Exercise in Rats


Cancellous bone formation response to simulated resistance training during disuse is blunted by concurrent alendronate treatment.

The purpose of this study was to assess the effectiveness of simulated resistance training (SRT) exercise combined with alendronate (ALEN) in mitigating or preventing disuse-associated losses in cancellous bone microarchitecture and formation. Sixty male Sprague-Dawley rats (6 months old) were randomly assigned to either cage control (CC), hind limb unloading (HU), HU plus either ALEN (HU + ALEN), SRT (HU + SRT), or a combination of ALEN and SRT (HU + SRT/ALEN) for 28 days. HU + SRT and HU + SRT/ALEN rats were anesthetized and subjected to muscle contractions once every 3 days during HU (four sets of five repetitions, 1000 ms isometric + 1000 ms eccentric). Additionally, HU + ALEN and HU + SRT/ALEN rats received 10 µg/kg of body weight of ALEN three times per week. HU reduced cancellous bone-formation rate (BFR) by 80%, with no effect of ALEN treatment (-85% versus CC). SRT during HU significantly increased cancellous BFR by 123% versus CC, whereas HU + SRT/ALEN inhibited the anabolic effect of SRT (-70% versus HU + SRT). SRT increased bone volume and trabecular thickness by 19% and 9%, respectively, compared with CC. Additionally, osteoid surface (OS/BS) was significantly greater in HU + SRT rats versus CC (+32%). Adding ALEN to SRT during HU reduced Oc.S/BS (-75%), Ob.S/BS (-72%), OS/BS (-61%), and serum TRACP5b (-36%) versus CC. SRT and ALEN each independently suppressed a nearly twofold increase in adipocyte number evidenced with HU and inhibited increases in osteocyte apoptosis. These results demonstrate the anabolic effect of a low volume of high-intensity muscle contractions during disuse and suggest that both bone resorption and bone formation are suppressed when SRT is combined with bisphosphonate treatment.

Swift JM, Swift SN, Nilsson MI, Hogan HA…
J. Bone Miner. Res. Sep 2011
PMID: 21509821