Changes of femoral periprosthetic bone mineral density 6 years after treatment with alendronate following total hip arthroplasty

Earlier osteodensitometric results of femoral periprosthetic bone showed that postoperative antiresorptive treatment with alendronate following total hip arthroplasty (THA) reduces the periprosthetic bone loss that commonly occurs in the first months after surgery. However, whether alendronate can prevent periprosthetic bone loss over the long term, or if bone loss occurs after discontinuing alendronate is unknown. Femoral periprosthetic bone mineral density (BMD) was assessed in 49 patients 6 years after cementless total hip arthroplasty using dual energy X‐ray absorptiometry. Twenty‐nine patients were treated postoperatively with alendronate and 20 control patients received no treatment. All patients were followed up at 12 months after surgery in a prospective randomized study. The bone mineral density was evaluated in 7 regions of interest according to the Gruen protocol. Six years after total hip arthroplasty, no significant changes were detected in femoral periprosthetic BMD when compared with results at 1 year, and the bone loss in patients with postoperative alendronate treatment was still significantly less than those without treatment. These results suggest that the prevention of femoral periprosthetic bone loss following THA achieved by postoperative antiresorptive treatment with alendronate is of long‐standing effect, and further bone loss does not occur after the first postoperative year. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:183–188, 2009     

Effect of pamidronate on bone turnover and implant migration after total hip arthroplasty: a randomized trial.

In this trial we studied the effect of pamidronate on periprosthetic bone turnover and pelvic implant migration over 2 years after hybrid total hip arthroplasty (THA). Twenty-two patients received 90 mg of pamidronate and 22 received placebo at randomization 5 days after surgery. Rapid periprosthetic bone loss occurred in the placebo group over the first 6 months and was accompanied by transient increases in biochemical markers of bone turnover. Partial recovery in bone mass occurred in most regions after this period. No recovery of bone mass occurred at the femoral calcar or the medial wall of the acetabulum. Femoral calcar bone loss at 2 years was strongly predicted by acute biomarker changes at week 6. Pamidronate therapy reduced femoral bone loss in the region of the femoral calcar (P = 0.01), but did not affect pelvic bone loss. Pamidronate therapy also inhibited the transient rise in biochemical markers of bone turnover during this period. Pamidronate therapy did not affect acetabular cup migration. Cup migration was inversely related to subject age, but unrelated to initial post-operative bone mineral density, or subsequent bone loss. In summary, early periprosthetic bone loss is associated with a transient expansion of the bone remodeling space. Bisphosphonate therapy reduces femoral calcar bone loss and bone turnover after THA, but did not influence cup migration in this study. Acute changes in biochemical markers predict femoral periprosthetic bone loss.     

Changes of the biochemical markers of bone turnover and periprosthetic bone remodeling after cemented hip arthroplasty

Do periprosthetic bone loss and postoperative levels of the biochemical markers of bone turnover correlate? The femoral bone mineral density of 53 patients was measured by dual-energy x-ray absorptiometry 1 week and 2, 4, 6, and 12 months after cemented total hip arthroplasty (THA). Biochemical markers of bone turnover were assayed preoperatively and 3, 8, 16, and 24 weeks post-THA. Greatest bone loss was detected in the calcar region (region of interest 7), on average, 16% after 1 year. A marker of bone resorption, C-terminal telopeptides of type I collagen, increased 21% 3 weeks after THA. A significant correlation between periprosthetic bone loss in region of interest 7 after 1 year and type I collagen at 3 weeks was seen (r = −0.42, P = .003). Data suggest that periprosthetic bone loss is induced by an early postoperative high activity of osteoclasts. Counteracting this osteoclast activity with a limited and timely postoperative antiresorptive treatment may be concluded for clinical application.     

Alendronate reduces periprosthetic bone loss after uncemented primary total hip arthroplasty: a prospective randomized study.

Periprosthetic bone loss, especially in the proximal part of the femur, is common after cemented and uncemented total hip arthroplasty (THA). Bone loss can be progressive and, in the extreme, may threaten survival of the prosthesis. To study whether alendronate therapy can reduce bone loss adjacent to prostheses, 13 uncemented primary THA patients were randomized to the study. They received 10 mg alendronate + 500 mg calcium (n = 8) or 500 mg calcium only (n = 5) daily for 6 months follow-up after THA. Periprosthetic bone mineral density (BMD) was measured with dual energy X-ray absorptiometry (DXA). Decreases in periprosthetic BMD in the alendronate-treated group were lower compared with the changes in the calcium-only group in the same regions of interest at the same follow-up time. In the proximal femur, the mean BMD decrease was 17.1% in the calcium-only group, whereas in the alendronate-treated group the decrease was only 0.9% (p = 0.019). The mean periprosthetic BMD change was also significantly different in the total periprosthetic area between the study groups at the end of the follow-up (calcium-only group -9.9% vs. alendronate-treated group -2.6%; p = 0.019). Alendronate therapy led to a significant reduction in periprosthetic bone loss after primary uncemented THA compared with the changes found in patients without therapy. This kind of bone response may improve the support of the prosthesis and may result in better survival of the prosthesis. However, in this study the follow-up time was too short and the study population was too small to make any long-term conclusions as to the prognosis for THA patients treated with alendronate.     

Bone mineral density and biochemical markers of bone turnover in aseptic loosening after total hip arthroplasty.

The aims of this study were to determine whether subjects with aseptic loosening after total hip arthroplasty (THA) have regional differences in periprosthetic bone mineral density (BMD) and systemic biochemical markers of bone turnover compared to subjects with successful implants.Proximal femoral and pelvic BMD were measured by dual energy X-ray absorptiometry and bone turnover markers were assayed in 49 subjects 12.6+/-4.3 (mean+/-SD) years after cemented THA. Femoral BMD was lower in Gruen zones 2, 5, 6, and 7 in subjects with a loose femoral implant (n=17) compared to those (n=32) with fixed femoral implants (P<0.05 all comparisons). This BMD difference was greatest (-31%, P=0.02) in the proximal and medial region of the femur. Subjects with femoral loosening had higher levels of the bone resorption marker N-telopeptides of type-I collagen (P=0.02) than those with a fixed femoral implant. No differences in pelvic BMD or bone turnover markers were found between subjects with loose (n=18) versus fixed (n=31) pelvic implants.This study suggests that failure of femoral components after cemented THA is associated with region-specific decreases in BMD and an increase in urinary excretion of N-telopeptide cross-links of type-I collagen. These surrogate outcome markers may be of value in monitoring response to antiresorptive therapies used to treat periprosthetic osteolysis, although the diagnosis of aseptic loosening remains clinical and radiological.     

地舒单抗对绝经后骨质疏松性股骨颈骨折全髋关节置换术后股骨近端假体周围骨密度的影响

目的:研究地舒单抗对绝经后骨质疏松性股骨颈骨折患者全髋关节置换术后(total hip arthroplasty,THA)股骨近端假体周围骨密度的影响。方法:选取2020年10月至2021年10月绝经后女性骨质疏松性股骨颈骨折行THA术后54例,治疗组25例接受地舒单抗治疗,年龄(74.3±6.2)岁;对照组29例未接受地舒单抗治疗,年龄(75.2±4.8)岁。术后1周及3、6及12个月各个时间点,通过双能X线骨密度仪(DEXA型)测定股骨近端假体周围骨密度,并在不同时间点测量骨转换各项指标。结果:术后3、6及12个月对照组的抗酒石酸酸性磷酸酶(tartrate resistant acid phosphatase,TRACP-5b)高于治疗组(P<0.05);对照组术后12个月骨特异性碱性磷酸酶(bone-specific alkaline phosphatase,BALP)高于治疗组(P<0.05)。两组患者Gruen 1、7区的骨密度在术后3、6及12个月较术后1周(基线)均下降(P<0.05);对照组Gruen 7区术后各时间点比较,差异有统计学意义(P<0.05);治疗组各时间点比较,差异无统计学意义(P>0.05)。两组术后3个月Gruen 1、7区比较,差异无统计学意义(P>0.05);术后6个月Gruen 1、7区和术后12个月Gruen 1、7区,治疗组骨密度均明显高于对照组(P<0.05)。两组术后3个月Gruen 1、7区骨密度下降百分比比较,差异无统计学意义(P>0.05)。对照组术后6个月Gruen 1、7区,术后12个月Gruen 1、7区骨密度下降百分比明显高于治疗组(P<0.05)。提示在使用地舒单抗6个月后,即可降低骨密度丢失幅度,并且该效应可达至术后12个月。结论:绝经后骨质疏松性股骨颈骨折患者在THA术后,使用地舒单抗可减少股骨近端假体周围骨密度丢失,有效抑制骨吸收。     

Alendronate inhibits periprosthetic bone loss around uncemented femoral components

Periprosthetic bone loss can be severe around the femoral component after uncemented arthroplasty. This study investigated the inhibitory effect of alendronate on periprosthetic bone loss. Seventeen patients underwent arthroplasty with an uncemented femoral component. Among them, 8 patients were given alendronate 5 mg once daily for 1 year (ALN group) and 9 patients received no pharmacotherapy (control group). Bone mineral density was measured in six periprosthetic zones by dual-energy X-ray absorptiometry at 1, 6, and 12 months after surgery. The average periprosthetic bone mineral density was 0.674–0.920 g/cm² at 1 month after surgery. From 6 months onward, the absolute bone mineral density and the ratio relative to the 1-month value were significantly decreased in the proximal zones of the femur in the control group (the ratio decreased from 0.817 to 0.769; P = 0.0040–0.0353). In the ALN group, however, the absolute and relative bone mineral density of the proximal femur remained unchanged for 12 months. In the other femoral zones, the absolute and relative bone mineral density remained unchanged throughout the study in both groups. We concluded that alendronate significantly inhibited the decrease of periprosthetic bone mineral density in the proximal femur after uncemented arthroplasty.     

Female patients with low systemic BMD are prone to bone loss in Gruen zone 7 after cementless total hip arthroplasty: A 2-year DXA follow-up of 39 patients

Background and purpose Factors that lead to periprosthetic bone loss following total hip arthroplasty (THA) may not only depend on biomechanical implant-related factors, but also on various patient-related factors. We investigated the association between early changes in periprosthetic bone mineral density (BMD) and patient-related factors.Patients and methods 39 female patients underwent cementless THA (ABG II) with ceramic-ceramic bearing surfaces. Periprosthetic BMD in the proximal femur was determined with DXA after surgery and at 3, 6, 12, and 24 months. 27 patient-related factors were analyzed for their value in prediction of periprosthetic bone loss.Results Total periprosthetic BMD was temporarily reduced by 3.7% at 3 months (p < 0.001), by 3.8% at 6 months (p < 0.01), and by 2.6% at 12 months (p < 0.01), but recovered thereafter up to 24 months. Preoperative systemic osteopenia and osteoporosis, but not the local BMD of the operated hip, was predictive of bone loss in Gruen zone 7 (p = 0.04), which was the only region with a statistically significant decrease in BMD (23%, p < 0.001) at 24 months. Preoperative serum markers of bone turnover predicted the early temporary changes of periprosthetic BMD. The other patient-related factors failed to show any association with the periprosthetic BMD changes.Interpretation Female patients with low systemic BMD show greater bone loss in Gruen zone 7 after cementless THA than patients with normal BMD. Systemic DXA screening for osteoporosis in postmenopausal patients before THA could be used to identify patients in need of prophylactic anti-resorptive therapy.     

The effectiveness of mono or combined osteoporosis drug therapy against bone mineral density loss around femoral implants after total hip arthroplasty

Several previous studies have reported that bone mineral density (BMD) loss around femoral implants is a common outcome, particularly in the proximal femur, after total hip arthroplasty (THA). The purpose of this study was to investigate the effectiveness of alendronate monotherapy and combined therapy using alendronate and alfacalcidol for BMD preservation around femoral implants after primary THA. This study series included 60 patients who were classified into monotherapy (alendronate alone) (n = 18), combined-therapy (alendronate and alfacalcidol) (n = 20) or non-medication (n = 22) groups. The periprosthetic BMD and profile of the biochemical markers such as bone-specific alkaline phosphatase and serum N-terminal telopeptides of type-1 collagen (NT_X) were measured at 1, 12, 24 and 48 weeks after surgery. The BMD values in the region of the calcar of monotherapy and combined-therapy patients were maintained and were significantly higher than those of non-medication patients at each measurement period. The plasma levels of NT_X in the monotherapy and combined-therapy groups were found to be significantly lower than those in the non-medication group at each measurement period. In conclusion, the monotherapy and combined-therapy regimens significantly prevent periprosthetic BMD loss around femoral implants, most notably in the calcar, compared to no medication.     

Prevention of bone loss in early nonsurgical and nonosteoporotic high turnover patients with salmon calcitonin: The role of biochemical bone markers in monitoring high turnover patients under calcitonin treatment

Annual bone loss rate was estimated in a group of randomly selected 150 nonsurgical and nonosteoporotic early postmenopausal women, 42–56 years, with the use of the mathematical equation proposed by Christiansen et al. (OSTEOTREND-R) [1]. Fifty-six women were characterized as high turnover patients (estimated annual bone loss more than 2.7%). These high turnover patients were included in a double-blind, placebo-controlled clinical study. Patients were divided into two groups of 28 women each. The first group of patients received 100 IU of salmon calcitonin intranasally daily for 1 year and the second group intranasal spray of placebo daily. Blood and urine biochemical parameters as well as bone mineral content of the spine and proximal forearm were determined initially and at the end of 6 and 12 months. No other side effects were noted apart from discomfort of nasal mucosa in two patients (one in each group). The group of calcitonin-treated patients showed a dramatic decrease in bone loss rate as estimated with the use of biochemical bone markers at the end of 6 and 12 months (3.7% versus 0.8% and 0.0% at the end of 6 and 12 months, respectively, P<0.001) whereas in the placebo group, bone loss rate remained unchanged (4.2% versus 4.1% and 4.3% at the end of 6 and 12 months, respectively). The calcitonintreated patients showed a significant increase in bone mineral content of spine and proximal forearm (P<0.001 at the end of 6 and 12 months, respectively). On the other hand, a significant decrease in all measurement sites appeared in the placebo group. In conclusion, our results showed that nasal salmon calcitonin administration can prevent the increased postmenorpausal bone loss in selected high bone turnover patients. The predicted annual bone loss rate, as estimated with the combination of biochemical bone markers, is useful in monitoring the responsiveness of high turnover patients to calcitonin at short intervals.     

Effect of robotic milling on periprosthetic bone remodeling.

The ROBODOC system has provided better fit and fill of the stem and less destruction of the bony architecture than with manual surgery. These benefits might affect femoral periprosthetic bone remodeling. We evaluated the effects of robotic milling in cementless total hip arthroplasty (THA) in a longitudinal 24-month follow-up study using dual energy X-ray absorptiometry (DEXA) and plain radiographs of 29 patients (31 hips) after ROBODOC THA and 24 patients (27 hips) after manual THA with the same stem design. To minimize the influence of other factors on bone remodeling, only female osteoarthritis patients, who had no drugs that might affect bone metabolism were enrolled. Significantly less bone loss occurred at the proximal periprosthetic areas in the ROBODOC group. In zone 1, the decrease was 15.5 versus 29.9% using conventional rasping; in zone 7, the loss was 17.0% with ROBODOC compared to 30.5% with conventional rasping (p < 0.05). On radiographs, endosteal spot welds in the proximal medial portion were more pronounced in the ROBODOC group (48 vs. 11% in the conventional group, p < 0.05). Our results suggest that robotic milling is effective in facilitating proximal load transfer around the femoral component and minimizing bone loss after cementless THA.     

Comparison of the Effect of Denosumab and Alendronate on BMD and Biochemical Markers of Bone Turnover in Postmenopausal Women With Low Bone Mass: A Randomized,Blinded, Phase 3 Trial

Denosumab is a fully human monoclonal antibody that inhibits bone resorption by neutralizing RANKL, a key mediator of osteoclast formation, function, and survival. This phase 3, multicenter, double‐blind study compared the efficacy and safety of denosumab with alendronate in postmenopausal women with low bone mass. One thousand one hundred eighty‐nine postmenopausal women with a T‐score ≤ ?2.0 at the lumbar spine or total hip were randomized 1:1 to receive subcutaneous denosumab injections (60 mg every 6 mo [Q6M]) plus oral placebo weekly (n = 594) or oral alendronate weekly (70 mg) plus subcutaneous placebo injections Q6M (n = 595). Changes in BMD were assessed at the total hip, femoral neck, trochanter, lumbar spine, and one‐third radius at 6 and 12 mo and in bone turnover markers at months 1, 3, 6, 9, and 12. Safety was evaluated by monitoring adverse events and laboratory values. At the total hip, denosumab significantly increased BMD compared with alendronate at month 12 (3.5% versus 2.6%; p < 0.0001). Furthermore, significantly greater increases in BMD were observed with denosumab treatment at all measured skeletal sites (12‐mo treatment difference: 0.6%, femoral neck; 1.0%, trochanter; 1.1%, lumbar spine; 0.6%, one‐third radius; p ≤ 0.0002 all sites). Denosumab treatment led to significantly greater reduction of bone turnover markers compared with alendronate therapy. Adverse events and laboratory values were similar for denosumab‐ and alendronate‐treated subjects. Denosumab showed significantly larger gains in BMD and greater reduction in bone turnover markers compared with alendronate. The overall safety profile was similar for both treatments.     

Alendronate has a residual effect on bone mass in postmenopausal Danish women up to 7 years after treatment withdrawal

Alendronate has been shown to reduce bone turnover and increase bone mass. However, little is known about the duration of the effect on bone after treatment withdrawal. The aim of this study was to investigate the long-term effects on bone mineral density (BMD) and bone turnover of various alendronate regimens after treatment withdrawal. In this study, we followed 203 postmenopausal women who previously participated in two alendronate randomized placebo-controlled trials. Daily oral treatment with various doses of alendronate (2.5-20 mg) were given for 2, 4, or 6 yr followed by no treatment for 7, 5, or 3 yr, respectively. Bone mineral density of the lumbar spine, hip, and forearm was measured by dual-energy x-ray absorptiometry. Biochemical markers of bone turnover were induced serum C-terminal telopeptides of type I collagen (CTX) and osteocalcin. Women who received alendronate (2.5-10 mg per day) for 2 yr had a 3.8% higher BMD compared to those receiving placebo when assessed 7 yr after withdrawal. The residual effect was proportionally larger in women who had received treatment for 4 (5.9%, P=0.02) or 6 yr (8.6%, P=0.002), respectively. However, the largest residual effect was found in women treated with alendronate 20 mg per day for 2 yr (9.7%, P=0.01 vs. placebo). The rate of bone loss after alendronate withdrawal was comparable to the bone loss observed in the placebo group. Bone markers tended to reverse back to normal levels, but were still affected even several years after withdrawal of treatment. This study has demonstrated that the efficacy of alendronate in preventing bone loss was proportional to the duration of treatment. The rate of bone loss after withdrawal of alendronate corresponded to the normal postmenopausal rate of bone loss. A residual effect on BMD was found up to 7 yr after treatment withdrawal.     

Restoration of proximal periprosthetic bone loss by denosumab in cementless total hip arthroplasty

Summary

Denosumab contributed to the restoration of proximal periprosthetic bone loss around the femoral stem that were measured using a DEXA, especially in zone 7, at 1 year after cementless THA in elderly osteoporotic patients.

Introduction

Although bone quality is an important issue in elderly osteoporotic patients who underwent total hip arthroplasty (THA) with a cementless stem, periprosthetic bone mineral density (BMD) in the proximal femur has been reported to be decreased by 15–40% postoperatively. Some authors have examined the use of several types of bisphosphonates to prevent decreases in BMD in the proximal femur after cementless THA; however, few reports have demonstrated success in restoring BMD in the proximal medial femoral bone, such as zone 7.

Methods

We conducted prospective study comparing patients who underwent cementless THA administered with denosumab (10 patients) and without denosumab (10 patients). BMD around the femoral stem were measured using a DEXA immediately after surgery, and at 6 months and at 1 year after surgery. No difference was found between the two groups referred to the patient’s demographic data.

Results

We found that denosumab displayed definitive effects in increasing the % change in periprosthetic BMD at zone 7 by an average of 7.3% in patients with cementless THA, compared to control group who were given only vitamin D.

Conclusion

Denosumab is one of a number of anti-osteoporotic agents to have a definitive effect on the restoration of proximal periprosthetic bone loss, especially in zone 7, after cementless THA. Denosumab contributed to the restoration of decreased periprosthetic BMD to normal levels. As the decrease in BMD in the proximal femur after THA is considered to be apparent at 6–12 months after surgery, it is believed that prevention of the deterioration of bone quality is important in the proximal femur immediately after cementless THA for elderly female patients with osteoporosis.

     

Treatment of Osteoporosis and Osteopenia in Long-term Renal Transplant Patients with Alendronate

Bone mineral density (BMD) and biochemical markers of bone-turnover were evaluated in a 2-year study in 58 long-term renal transplant recipients with good renal function. In the first year of study, data were collected and patients with osteoporosis and parameters of high bone turnover were classified as being at high risk for on-going bone loss (Group A; n = 29). Patients with lesser degrees of bone loss or without biochemical parameters of high bone turnover were followed longitudinally (Group B; n = 29). Group A patients were then placed on alendronate 10mg/day and both groups were followed for an additional year. Changes in regional BMD and bone-turnover markers between the first and second year within each group were analyzed using paired tests. BMD in Group A, which had declined at the lumbar spine (- 1.6 +/- 0.5%) and total femur (-1.5 +/- 0.4%) during the first year of the study, increased on alendronate therapy at both the lumbar spine (+3.4 +/- 0.6%, p = 0.001) and total femur (+1.6 +/- 0.6%, p <0.001). These patients also experienced a significant decline in levels of serum alkaline phosphatase, osteocalcin, urinary levels of deoxypyridinoline and pyridinoline. In contrast, neither BMD nor biochemical markers changed significantly over 2 years in Group B. The current results demonstrate that renal transplant patients with osteoporosis and biochemical parameters of high bone turnover are at continued risk for bone loss. Therapy with a bisphosphonate can reverse this bone loss and even increase bone mass in these patients. Whether patients with lesser degrees of bone loss and/or patients without parameters of high bone turnover can also benefit from bisphosphonate therapy deserves further study.     

Treatment with once-weekly alendronate 70 mg compared with once-weekly risedronate 35 mg in women with postmenopausal osteoporosis: a randomized double-blind study.

Once-weekly alendronate 70 mg and once-weekly risedronate 35 mg are indicated for the treatment of postmenopausal osteoporosis. These two agents were compared in a 12-month head-to-head trial. Greater gains in BMD and greater reductions in markers of bone turnover were seen with alendronate compared with risedronate with similar tolerability. INTRODUCTION: The nitrogen-containing bisphosphonates, alendronate and risedronate, are available in once-weekly (OW) formulations for the treatment of postmenopausal osteoporosis. A 12-month, head-to-head study was performed to compare these agents in the treatment of postmenopausal women with low BMD. MATERIALS AND METHODS: A total of 1053 patients from 78 U.S. sites were randomized to OW alendronate 70 mg (N = 520) or risedronate 35 mg (N = 533), taken in the morning after fasting. Endpoints included BMD changes over 6 and 12 months at the hip trochanter, total hip, femoral neck, and lumbar spine (LS); percent of patients with predefined levels of change in trochanter and LS BMD at 12 months; and change in biochemical markers of bone turnover at 3, 6, and 12 months. Tolerability was evaluated by adverse experience (AE) reporting. RESULTS: Significantly greater increases in hip trochanter BMD were seen with alendronate (3.4%) than risedronate (2.1%) at 12 months (treatment difference, 1.4%; p < 0.001) as well as 6 months (treatment difference, 1.3%; p < 0.001). Significantly greater gains in BMD were seen with alendronate at all BMD sites measured (12-month difference: total hip, 1.0%; femoral neck, 0.7%; LS, 1.2%). Significant differences were seen as early as 6 months at all sites. A greater percentage of patients had > or =0% (p < 0.001) and > or =3% (p < 0.01) gain in trochanter and spine BMD at 12 months with alendronate than risedronate. Significantly greater (p < 0.001) reductions in all biochemical markers of bone turnover occurred with alendronate compared with risedronate by 3 months. No significant differences were seen between treatment groups in the incidence of upper gastrointestinal AEs or AEs causing discontinuation. CONCLUSIONS: In this 12-month, head-to-head trial of alendronate and risedronate, given in accordance with the approved OW regimens for treatment of osteoporosis in postmenopausal women, alendronate produced greater gains in BMD and greater reductions in markers of bone turnover than risedronate. The greater antiresorptive effect of alendronate was seen as early as 3 months, and the tolerability profiles were similar.     

Effect of pamidronate on excretion of pyridinium crosslinks of collagen after total hip arthroplasty

Periprosthetic bone loss is an important factor that limits implant survival after total hip arthroplasty (THA). In a randomized trial we previously reported that pamidronate therapy prevented periprosthetic bone loss and decreased urinary excretion of N-telopeptide collagen cross-links over the first 6 months after THA, but had no apparent effect on free deoxypyridinoline excretion (J Bone Miner Res 2001; 16:556–564). In this study we investigated this discrepant observation that pamidronate reduced conjugated cross-link excretion but had no effect on free cross-links. Free and total deoxypyridinoline (DPD) were assayed by reverse-phase high-performance liquid chromatography (HPLC) and by immunosorbent assay (ELISA) at preoperative baseline and at week 6 after surgery in 46 subjects who had taken part in the trial. Randomly selected, 22 subjects received a single 90 mg intravenous infusion of pamidronate and 24 received placebo. Acute rises in free and total DPD occurred in both study groups at week 6 (P < 0.05). Total DPD excretion was lower in the pamidronate group than in the placebo group when measured by both HPLC and ELISA (P < 0.05). No difference in free DPD was found between groups. A rise in the ratio of free to total DPD occurred in the pamidronate group at week 6 (P = 0.03), but not in the placebo group. Pamidronate treatment suppresses excretion of total DPD. This is consistent with the effect of pamidronate on other turnover markers and periprosthetic bone loss after THA. Urinary-free DPD is a poor marker of response to treatment as the ratio of free-to-total cross-links is affected by amino-bisphosphonate therapy.     

Zoledronic acid initiated during the first year of androgen deprivation therapy increases bone mineral density in patients with prostate cancer

PURPOSE: Androgen deprivation therapy in patients with prostate cancer is associated with bone loss and an increased risk of fractures. Zoledronic acid protects against bone mineral density loss when initiated concurrently with androgen deprivation therapy. We evaluated the effect of zoledronic acid initiated subsequent to androgen deprivation therapy on bone mineral density and biochemical markers of bone turnover. MATERIALS AND METHODS: Patients with prostate cancer without bone metastases who had received androgen deprivation therapy for 12 months or less were randomized to 4 mg zoledronic acid or placebo intravenously every 3 months for 1 year. Patients were stratified according to androgen deprivation therapy duration (less than 6 vs 6 to 12 months). The primary end point was the change in femoral neck and lumbar spine bone mineral density in the 2 groups. The secondary end point was the change in serum bone specific alkaline phosphatase and urine N-telopeptide levels. Total hip bone mineral density was also measured. RESULTS: The 120 patients with prostate cancer received zoledronic acid (61) or placebo (59). Compared with placebo, zoledronic acid increased femoral neck, total hip and lumbar spine bone mineral density yearly by 3.6% (p = 0.0004), 3.8% (p <0.0001) and 6.7% (p <0.0001), respectively. The effects of zoledronic acid on bone mineral density at these 3 sites were not differentiated according to androgen deprivation therapy duration. Additionally, mean bone specific alkaline phosphatase and N-telopeptide levels were decreased in the zoledronic acid group (each p <0.0001) and were increased in the placebo group (p <0.0001 and p = 0.004, respectively). CONCLUSIONS: Zoledronic acid increased bone mineral density and suppressed bone turnover markers in patients with prostate cancer without bone metastases when initiated during year 1 of androgen deprivation therapy.     

Alendronate prevents bone loss in Chinese women with osteoporosis

The objectives of the Hong Kong study are to investigate the efficacy of 10 mg alendronate in preventing bone loss at the hip and spine in osteoporotic Chinese women. One hundred osteoporotic Chinese women, aged 60-79 years, were randomized to receive 10 mg of alendronate or placebo, with 500 mg elemental calcium. Bone mineral density (BMD) at the spine and hip were measured at baseline, 6 months, and 12 months. Seventy-eight subjects completed the study. The alendronate-treated group gained more bone at both the spine (p < 0.01) and femoral neck (p < 0.001), with a mean difference (+/-SE) of 2.4% (+/-0.86%) at the spine and 3.98% (+/-0.95%) at the femoral neck. Of the 100 patients, 6 subjects in the alendronate group and 5 subjects in the placebo group had mild gastrointestinal symptoms. We conclude that alendronate (10 mg) was effective in preventing bone loss in postmenopausal osteoporotic Chinese women.     

Effect of alendronate on bone mineral density and bone turnover in Thai postmenopausal osteoporosis

Alendronate has recently been approved for the prevention and treatment of postmenopausal osteoporosis, and its efficacy has been demonstrated in many Western countries. Our present study was performed to evaluate the effect of alendronate on bone mineral density (BMD) and its tolerability in Thais. Eighty postmenopausal women with osteoporosis participated in this study. After giving informed consent, the subjects were randomly allocated either 10mg alendronate or placebo in a double-blind fashion. All patients received a supplement of 500mg elemental calcium daily. BMD at the lumbar spine, femoral neck, and distal forearm was measured at baseline and 6 and 12 months after treatment. Biochemical markers of bone resorption were determined at baseline and 6 months after treatment. Baseline characteristics were similar in both alendronate- and placebo-treated groups. Ten subjects discontinued the study. Of 70 subjects, 32 received 10mg alendronate daily and the remaining subjects received placebo. At 1 year, BMD in the alendronate-treated group had increased from baseline by 9.2%, 4.6%, and 3.1% at lumbar spine, femoral neck, and distal forearm, respectively. These percentages were greater than those in controls (4.1%, 0.6%, and 1.0%, respectively). Urinary N-terminal telopeptide (NTx)-I and serum C-terminal telopeptide (CTx)-I levels decreased in both groups after 6 months of treatment. However, more reduction was demonstrated in the alendronate-treated group (71.9% vs. 28.4%, P 0.01, and 84.7% vs. 33.1%, P 0.01, respectively). Compliance with treatment and drug tolerability were good in both alendronate and placebo groups. We concluded that treatment with alendronate 10mg daily for Thai postmenopausal women with osteoporosis significantly increased BMD at all skeletal sites and reduced biochemical markers of bone resorption. It was well tolerated without any serious side effects.