Influence of forces on peri-implant bone

Abstract: Occlusal forces affect an oral implant and the surrounding bone. According to bone physiology theories, bones carrying mechanical loads adapt their strength to the load applied on it by bone modeling/remodeling. This also applies to bone surrounding an oral implant. The response to an increased mechanical stress below a certain threshold will be a strengthening of the bone by increasing the bone density or apposition of bone. On the other hand, fatigue micro-damage resulting in bone resorption may be the result of mechanical stress beyond this threshold. In the present paper literature dealing with the relationship between forces on oral implants and the surrounding bone is reviewed. Randomized controlled as well as prospective cohorts studies were not found. Although the results are conflicting, animal experimental studies have shown that occlusal load might result in marginal bone loss around oral implants or complete loss of osseointegration. In clinical studies an association between the loading conditions and marginal bone loss around oral implants or complete loss of osseointegration has been stated, but a causative relationship has not been shown.     

Evaluation of peri-implant bone loss around platform-switched implants

This clinical and radiographic prospective study evaluated bone loss around two-piece implants that were restored according to the platform-switching protocol. One hundred thirty-one implants were consecutively placed in 45 patients following a nonsubmerged surgical protocol. On 75 implants, a healing abutment 1 mm narrower than the implant platform was placed at the time of surgery. On the remaining implants, a healing abutment of the same diameter as the implant was inserted. All implants were positioned at the crestal level. Clinical and radiographic examinations were performed prior to surgery, at the end of surgery, 8 weeks after implant placement, at the time of provisional prosthesis insertion, at the time of definitive prosthesis insertion, and 12 months after loading. The data collected showed that vertical bone loss for the test cases varied between 0.6 mm and 1.2 mm (mean: 0.95 +/- 0.32 mm), while for the control cases, bone loss was between 1.3 mm and 2.1 mm (mean: 1.67 +/- 0.37 mm). These data confirm the important role of the microgap between the implant and abutment in the remodeling of the peri-implant crestal bone. Platform switching seems to reduce peri-implant crestal bone resorption and increase the long-term predictability of implant therapy.     

2种不同种植体植入对种植体周围软组织的影响

目的: 研究2种种植体对种植体周围软组织的影响。方法: 选择2020年12月—2021年2月普陀区眼病牙病防治所收治的单颗后牙缺失且需行种植修复的患者40例,其中植入骨水平种植体10例,软组织水平种植体30例。在完成种植冠修复当天、3个月、6个月及12个月时比较2组种植体的探诊深度,检测种植体龈沟液中天冬氨酸转氨酶（AST）和碱性磷酸酶（ALP）水平。采用SPSS 17.0软件包对数据进行统计学分析。结果: 修复完成当天、3个月、6个月及12个月,软组织水平种植体的探诊深度和ALP水平均显著低于骨水平种植体（P<0.05）。其中修复完成当天,软组织水平种植体的AST显著低于骨水平种植体（P<0.05）。随着时间增加,骨水平种植体龈沟液中的AST迅速降低,最后与软组织水平种植体接近（P>0.05）。结论: 尽管骨水平种植体和软组织水平种植体均具有良好的临床使用效果,但软组织水平种植体周围的软组织表现出更好的稳定性。     

Mandibular fracture caused by peri-implant bone loss: report of a case

BACKGROUND: A major complication related to excessive bone loss around implants is fracture of the mandible. This complication is most likely to occur in a very atrophic mandible. A 57-year-old woman presented with progressive pain and swelling that had been present for 5 days in the right frontal region of the mandible. An intraoral radiograph revealed a radiolucency around one of the implants in the interforaminal region. METHODS: Ten years earlier, 4 hollow-screw implants of 10 mm length had been inserted in the interforaminal region of the edentulous mandible. Throughout the 10-year postoperative period, no adverse clinical events were seen; however, during the last 7 years, no radiographic follow-up was performed. Mobility was tested after removal of the bar, on which one of the implants appeared to be mobile. The mobile implant was removed together with the fibrous tissue. RESULTS: At a recall visit 2 weeks later, a radiograph revealed a fracture of the mandible at the explantation site. Characteristic features of the hollow-screw implant are the hollow body and the transverse openings in the side walls of the implant. It has been reported that these characteristic features can enhance infection and rapid bone loss, but a case of mandibular fracture has never been described. CONCLUSION: Radiographs should be taken on a regular and perhaps more frequent basis to diagnose excessive bone loss, so that measures can be taken to prevent the risk of mandibular fracture.     

Platform switching and matrix metalloproteinase-8 levels in peri-implant sulcular fluid

Objectives: The concept of platform switching has been introduced to implant therapy, however long‐term data are sparse. The aim of this study was to biochemically investigate the inflammatory response mediated by MMP‐8 to platform switching after 3 years of loading, in order to understand the long‐term effect of implant/abutment mismatching on peri‐implant health. Methods: A total of 70 implants had been inserted in the posterior maxilla in 26 patients and were randomly assigned to one of the four treatment regimens (implant diameter 3.8 [control group], 4.3 [Test group 1, T₁], 4.8 [Test group 2, T₂] and 5.5 mm [Test group 3, T₃]). All implants were restored using a 3.8 mm abutment. In the test groups, this restoration resulted in a mismatching of 0.25–0.85 mm of implant–abutment diameters. Results: Thirty‐six months after prosthetic rehabilitation, peri‐implant sulcular fluid samples were taken from two aspects of all implants and from periodontally healthy adjacent teeth. Samples were processed in a conventional ELISA using monoclonal antibodies recognizing the active entity of MMP‐8. In the test groups, MMP‐8 mean values were 2.76 ng for T₁ (SD: 2.91), 3.30 ng for T₂ (SD: 1.94) and 3.18 ng for T₃ (SD: 2.46). For the control group, MMP‐8 mean value was 3.6 ng (SD: 2.23), whereas 3.38 ng (SD: 2.2) was recorded at the adjacent teeth. There were no statistically significant differences in MMP‐8 values between the groups (P=0.113, Kruskal–Wallis). Conclusions: The presence of an implant/abutment mismatching specific for this prosthetic concept is compatible with long‐term peri‐implant health as demonstrated by analysis of a sensitive biomarker of the peri‐implant inflammatory response.     

Nine- to fourteen-year follow-up of implant treatment. Part III: factors associated with peri-implant lesions

OBJECTIVE: The aim of the present paper was to analyse, on patient and implant basis, factors related to peri-implant lesions. MATERIAL AND METHODS: Two hundred and eighteen patients treated with titanium implants were examined for biological complications at existing implants 9-14 years after initial therapy. The effects of several potentially explanatory variables, both on patient and on implant levels, were analysed. RESULTS: On the implant level, the presence of keratinized mucosa (p = 0.02) and plaque (p = 0.005) was associated with mucositis (probing depth > or =4 mm + bleeding on probing). The bone level at implants was associated with the presence of keratinized mucosa (p = 0.03) and the presence of pus (p < 0.001). On the patient level, smoking was associated with mucositis, bone level and peri-implantitis (p = 0.02, <0.001 and 0.002, respectively). Peri-implantitis was related to a previous history of periodontitis (p = 0.05). CONCLUSIONS: Individuals with a history of periodontitis and individuals who smoke are more likely to develop peri-implant lesions.     

Impact of implant overloading on the peri-implant bone in inflamed and non-inflamed peri-implant mucosa

OBJECTIVE: To assess the impact of overloading on peri-implant bone level and the bone-to-implant contact (BIC) in the presence of healthy or inflamed peri-implant tissues. MATERIALS AND METHODS: Four screw-shaped machined implants were placed bilaterally in the mandible of four beagle dogs and left submerged for 3 months. Prosthetic abutments were connected either in supra-occlusal contact with the opposite teeth (overloaded) or in infra-occlusal position (unloaded). In each dog, cotton floss ligatures were placed unilaterally around abutments to promote plaque accumulation; the contralateral side was brushed three times a week. There were four experimental sites, two implants in each: loaded uninflamed (LU), loaded inflamed (LI), unloaded uninflamed (UU), and unloaded inflamed (UI). Clinical and radiographic parameters were recorded at baseline and every 3 months throughout the observation period. At 12 months, the dogs were sacrificed and histomorphometric analysis was performed. RESULTS: Implants with ligature-induced peri-implantitis presented high inflammatory indices throughout the observation period. Clinical parameters did not change from baseline for both LU and UU. Loading significantly increased the percentage of BIC (BIC%) (P<0.05) and slightly increased crestal bone resorption, but not apical to the implant neck. Both LI and UI groups showed significant peri-implant bone loss (P<0.01), mostly horizontal on the buccal aspect and angular on the lingual aspect, which exposed implant threads. Loading significantly (P<0.05) increased implant thread exposure due to buccal and lingual vertical bone resorption. CONCLUSIONS: In the presence of uninflamed peri-implant mucosa, overloading of implants in the dog model increased BIC% and slightly reduced marginal bone level. However, resorption did not progress beyond the implant neck. Overloading aggravated the plaque-induced bone resorption when peri-implant inflammation was present.     

Biomaterials, biocompatibility, and peri-implant considerations

There are series of tests recommended for evaluation of dental implants. These materials and instrumentation coupled with the publications reviewed here that deal with animal experimentation and implant experience in humans provide an outline of data that have made tissue response to dental implants more clearly delineated. However, there are several specific aspects of cellular response that remain to be illuminated and correlated with clinical and radiographic signs. The further study of the interface zone with corresponding characterization of materials will produce the final chapter in the development of this most interesting area of dentistry. As stated, no epithelial attachment to any dental implant post has been comprehensively described that utilizes light and electron microscopy or histochemistry. Rather, a concept of a biologic seal has emerged that delineates the external milieu of the mouth with its microbiota and plaque from the internal milieu of bone and connective tissue, where true osseointegration can and does take place.     

Titanium deposition after peri-implant care with the carbon dioxide laser

PURPOSE: Titanium endosseous implants are becoming increasingly important in dentistry because of their excellent long-term results. However, it has been reported that these implants may lead to higher concentrations of titanium, especially in the lungs and kidneys. The purpose of this study, therefore, was to determine whether CO2 laser-assisted decontamination of exposed implant surfaces is associated with an increase in titanium release. MATERIALS AND METHODS: In 6 beagle dogs, a total of 60 implants were placed. After osseointegration and second-stage surgery, peri-implantitis was induced by cotton floss ligatures for 12 weeks. Surgical treatment consisted of granulation tissue removal, including decontamination of the implant surface with 3 different methods. Twenty implants were decontaminated conventionally by an air-powder abrasive for 60 seconds. Another 20 implants were decontaminated by laser treatment alone. The last 20 implants were treated conventionally by air-powder abrasive and then lased. Four months later, fresh tissue samples of various tissues were evaluated by histologic and chemical analysis. RESULTS: Quantitative analysis indicated that titanium accumulation could be detected, especially in the spleen, liver, oral mucosa, regional lymph nodes, lung, and kidney in the beagle dog model. DISCUSSION: The concentrations found did not exceed those previously reported in the literature. CONCLUSION: These results support the hypothesis that CO2 laser-assisted therapy of ailing implants will not result in excessive titanium concentrations in tissues. Accordingly, CO2 lasers appear suitable and safe for peri-implant gingival surgery.     

Dimensions of peri-implant mucosa: an evaluation of maxillary anterior single implants in humans

BACKGROUND: Attempts have been made to evaluate the biologic dimension of osseointegrated implants, however, most are histologic studies in animals, and the effect of soft tissue support from adjacent teeth on the interproximal dimension of the peri-implant mucosa for anterior single implants has not been addressed. This study clinically evaluated the dimensions of the peri-implant mucosa around 2-stage maxillary anterior single implants in humans after 1 year of function. The influence of the peri-implant biotype was also examined. METHODS: Forty-five patients (20 males and 25 females) with a mean age of 47.3 years were included in this study. A total of 45 maxillary anterior single implant crowns with a mean functional time of 32.5 months (range, 12 to 78) were evaluated. The dimensions of peri-implant mucosa were measured by bone sounding using a periodontal probe at the mesial (MI), mid-facial (F), and distal (DI) aspects of the implant restoration and the proximal aspects (MT, DT) of adjacent natural teeth. In addition, the peri-implant biotype was evaluated and categorized as thick or thin. Statistical analysis was performed using an independent t test (P<0.05). RESULTS: The means and standard deviations of the dimensions of peri-implant mucosa at MT, MI, F, DI, and DT were 4.20 +/- 0.77 mm, 6.17 +/- 1.27 mm, 3.63 +/- 0.91 mm, 5.93 +/- 1.21 mm, and 4.20 +/- 0.64 mm, respectively. The dimensions of peri-implant mucosa in the thick biotype were significantly greater than the thin biotype at MT, MI, and DT (P<0.05). CONCLUSIONS: The mean facial dimension of peri-implant mucosa of 2-stage implants is slightly greater than the average dimension of the dentogingival complex. The level of the interproximal papilla of the implant is independent of the proximal bone level next to the implant, but is related to the interproximal bone level next to the adjacent teeth. Greater peri-implant mucosal dimensions were noted in the presence of a thick peri-implant biotype as compared to a thin biotype.     

Effect of platform switching on peri-implant bone levels: a randomized clinical trial

Objective: The concept of platform switching has been introduced to implant dentistry based on observations of reduced peri‐implant bone loss. However, randomized clinical trials are still lacking. This study aimed to test the hypothesis that platform switching has a positive impact on crestal bone‐level changes. Material and methods: Two implants with diameters of 4 mm were inserted epicrestally into one side of the posterior mandibles of 25 subjects. After 3 months of submerged healing, the reentry surgery was performed. On the randomly placed test implant, an abutment 3.3 mm in diameter was mounted, resulting in a horizontal circular step of 0.35 mm (platform switching). The control implant was straight, with an abutment 4 mm in diameter. Single‐tooth crowns were cemented provisionally. All patients were monitored at short intervals over the course of 1 year. Standardized radiographs and microbiological samples from the implants' inner spaces were obtained at baseline (implant surgery), and after 3, 4, and 12 months. Results: After 1 year, the mean radiographic vertical bone loss at the test implants was 0.53±0.35 mm and at the control implants, it was 0.58±0.55 mm. The mean intraindividual difference was 0.05±0.56 mm, which is significantly <0.35 mm (P=0.0093, post hoc power 79.9%). The crestal bone‐level changes depended on time (P<0.001), but not on platform switching (P=0.4). The implants' internal spaces were contaminated by bacteria, with no significant differences in the total counts between the test and the control at any time point (P=0.98). Conclusions: The present randomized clinical trial could not confirm the hypothesis of a reduced peri‐implant bone loss at implants restored according to the concept of platform switching. To cite this article:
Enkling N, Jöhren P, Klimberg V, Bayer S, Mericske‐Stern R, Jepsen S. Effect of platform switching on peri‐implant bone levels: a randomized clinical trial.
Clin. Oral Impl. Res. 22 , 2011; 1185–1192.
doi: 10.1111/j.1600‐0501.2010.02090.x     

A prospective multicenter study using two different surgical approaches in the mandible with turned Brånemark implants: conventional loading using fixed prostheses

Background: The use of a submerged implant system in a nonsubmerged surgical procedure has been reported to have promising results. At the time this study was initiated, no prospective, comparative studies with randomization between submerged and nonsubmerged surgical techniques had been published. Purpose: To evaluate the submerged and nonsubmerged surgical techniques when treating mandibular edentulism using a submerged implant system, with regard to implant survival and complications. Materials and Methods: A total of 77 patients were included and treated at nine clinics in Sweden and Norway. In total, 404 Brånemark System implants (standard and MkII implants) were inserted in the edentulous mandible; 198 implants according to the nonsubmerged protocol and 206 implants according to the traditional submerged procedure. The follow‐up period was up to 36 months after prosthesis insertion. Results: In the nonsubmerged group, 17 implants out of 198 implants (8.6%) were lost and in the submerged group, 5 out of 206 implants (2.4%) were lost. All implant failures occurred before the delivery of the final prosthesis. No major complications were reported during the implant surgery. However, at the clinical check‐up postoperatively and at the abutment connection surgery, 6 patients in the nonsubmerged group complained of pain at the implant sites, whereas there were no complaints of pain in the submerged group. Conclusions: The results of this study suggest that a turned Brånemark implant designed for a submerged implant placement procedure can be used in a nonsubmerged procedure and may be as predictable as the conventional submerged approach.     

The reaction of peri-implant tissues to titanium alloy and apatite-coated implants during the healing phase

Oral implantation has been a controversial dental therapeutic procedure. Many implant materials and designs are presently in progress of study to evaluate the long term response of peri-implant tissues, together with anticipated loading considerations. The purpose of this examination was to make clear whether a fibrous layer would form between bone and Titanium alloy and apatite-coated Titanium implants under stressed and unstressed conditions, during the healing phase after implantation. The in vivo evaluation of 10 implants were made on two dogs. The upper 2nd and 3rd and lower 3rd and 4th premolar teeth were extracted and the sockets allowed to heal for 3 months. The implants in the unstressed condition were completely submerged, and in the stressed condition they were left with their top 2 mm above the surface of the bone, so that after suturing the top of the implant was exposed to the oral environment. After the postoperative healing phase of 3 months, the animals were killed and the specimens were prepared for histological, SEM examinations and EDX analysis of the interface zone between bone and the implants. Histological examination showed a direct contact between the apatite-coated implant and new bone, so that the implant became anchored to bone without an intervening soft tissue layer and a similar result was obtained between the Titanium implant and bone in the unstressed condition. However the high magnification electron micrographs showed a thin connective tissue between the bead-blasted surface of the Titanium implant and bone, and this peri-implant tissue could be detached from the implant. In the stressed condition, a thin layer of fibrous tissue was interposed between the Titanium implant and bone. The high magnification electromicroscopical views of the interface zone between the bone and these implants showed coarse fiber bundles developed perpendicular to the Titanium surface and their terminal ends were confluent with the rugged Titanium surface presumably as a result of micro-movement during the 3 months healing phase. In this study, an adequate space for a development of fibro-anchorage was about 20-200 microns in width. If occlusal stresses were within permissible range in healing period, the relative motion of the implant and bone was then optimal for the formation of a fibro-anchorage. It could be suggested that an ideal stress transfer from the Titanium implant to bone might be achieved by this fibro-anchorage.     

种植体周围软组织质量对于边缘骨吸收的影响研究进展

影响种植体周围边缘骨吸收的因素有很多,种植体周围的软组织质量是其中很重要的一项.种植体周围的软组织质量可以应用角化黏膜宽度(keratinized mucosa width,KMW)、黏膜厚度(mucosa thickness,MT)和骨嵴上软组织高度(supracrestal tissue height,STH)等参...     

Nine- to fourteen-year follow-up of implant treatment. Part II: presence of peri-implant lesions

OBJECTIVES: The aim of this study was to analyse the proportions of peri-implant lesions at implants after 9-14 years of function. MATERIAL AND METHODS: Two hundred and ninety-four patients underwent implant therapy during the years 1988-1992 in Kristianstad County. These individuals were recalled to the speciality clinic 1 and 5 years after placement of the suprastructure. Between 2000 and 2002, 218 patients with 999 implants were examined clinically and radiographically. RESULTS: Forty-eight per cent of the implants had probing depth > or =4 mm and bleeding on probing (peri-implant mucositis). In 20.4% of the implants, the bone level was located 3.1 mm apical to the implant shoulder. Progressive bone loss (> or =1.8 mm) during the observation period was found in 7.7% of the implants. Peri-implantitis defined as bone loss > or =1.8 mm compared with 1-year data (the apical border of the bony defect located at or apical to the third thread, i.e. a minimum of 3.1 mm apical to the implant shoulder), combined with bleeding on probing and or pus, were diagnosed among 16% of the patients and 6.6% of the implants. CONCLUSION: After 10 years in use without systematic supportive treatment, peri-implant lesions is a common clinical entity adjacent to titanium implants.     

3I和奥齿泰种植体系统周围组织稳定性差异的临床对比研究

目的：探讨3I种植体和奥齿泰种植体修复后对种植体周围软硬组织的影响，为临床种植系统的选择提供临床依据。方法随机选取单牙缺失需种植修复的患者42例，分别行3I种植体（23枚）和奥齿泰种植体（26枚）种植修复，于修复后3、6、9和12个月测量种植体周围骨吸收、龈沟出血指数（sulcus bleeding index， SBI）、菌斑指数（plaque index，PLI）、探诊深度（probing depth，PD）、种植体周围龈沟液（peri?implant crevicular fluid ，PICF）的天冬氨酸转氨酶（aspartate aminotransferase ，AST）水平，并选取对侧健康牙作为对照。结果种植体修复后1年，种植体颈部骨组织呈现不断吸收趋势，且奥齿泰种植体骨吸收量大于3I种植体（P <0.05）。在修复后6、9和12个月，3I种植体SBI、PLI均低于奥齿泰种植体（P<0.05），3I种植体AST水平与天然牙差异无统计学意义，而奥齿泰种植体AST水平高于天然牙（P<0.05）。修复后9、12个月，3I种植体PD明显低于奥齿泰种植体（P<0.05）。结论3I种植体对种植体周围骨组织及周围牙龈组织的影响较奥齿泰小，但两者在研究期内均表现出良好的临床效果。     

Gene expression of inflammation and bone healing in peri-implant crevicular fluid after placement and loading of dental implants. A kinetic clinical pilot study using quantitative real-time PCR

Purpose: Early detection of healing complications after placement of dental implants is a pressing but elusive goal. This paper proposes a non‐invasive diagnostic tool for monitoring healing‐ and peri‐implant disease specific genes, complementary to clinical evaluations. Material and Methods: Eighteen partially edentulous patients were recruited to this pilot study. Three Brånemark TiUnite® implants/patient (Nobel Biocare) were placed in a one‐stage procedure. Abutments with smooth or rough (TiUnite®) surface were placed. The test group (n = 9) received fixed bridges (immediate loading), whereas the control group (n = 9) implants were loaded 3 months after surgery. In addition to clinical measurements, crevicular fluid was collected using paper strips at the implant abutments 2, 14, 28, and 90 days postoperative. mRNA was extracted, purified, and converted to cDNA. Quantitative PCR assays for IL‐1β, TNF‐α, Osteocalcin (OC), Alkaline Phosphatase (ALP), Cathepsin K, Tartrate Resistant Acid Phosphatase, and 18S ribosomal RNA were designed and validated. Relative gene expression levels were calculated. Results: One implant was lost in the control group and three in the test group. In one test patient, one implant showed lowered stability after 2 to 4 weeks and was unloaded. Later implant stability improved which allowed for loading after 3 to 4 months. TNF‐α and ALP most commonly showed correlation with clinical parameters followed by IL‐1β and OC. The strongest correlation was found for TNF‐α with clinical complications at 2 and 14 days (p = .01/r = ?048, and p = .0004/r = ?0.56, respectively; test and control groups together). In some cases, gene expression predicted clinical complications (TNF‐α, ALP, CK). Conclusion: This study is based on samples from few individuals; still, some genes showed correlation with clinical findings. Further studies are needed to refine and optimize the sampling process, to find the appropriate panel, and to validate gene expression for monitoring implant healing.     

牙种植体周围微生物研究

牙种植术是目前修复牙列缺损和牙列缺失的主要治疗方案,但是种植体周围微生态失衡易造成种植体周围疾病的发生,进而导致种植失败。从20世纪80年代开始,种植体周围微生物的研究就成为了口腔微生物研究的热点之一。正常种植体周围微生物和种植体周围炎症相关微生物存在着差异,这些差异直接或间接增加了种植体周围疾病的风险,因此寻找种植体周围黏膜炎和种植体周围炎“核心微生物组”是目前研究的关键。     

Calprotectin and cross-linked N-terminal telopeptides in peri-implant and gingival crevicular fluid

In a previous study on guided bone augmentation, a new collagen membrane was compared with an e-PTFE one on 28 partially edentulous patients who received 50 dental implants at stage 2 surgery. After implant integration and subsequent loading, we were able to recruit 22 patients with 22 implants and their contra-lateral corresponding teeth for longitudinal observation. Clinical parameters probing depth (PD), bleeding on probing (BoP), plaque index (PI), assessment of gingival crevicular fluid (GCF) and peri-implant crevicular fluid (PCF) volumes and periapical radiographs were performed at 2- and 3-year control appointments. Calprotectin (MRP 8/14) and cross-linked N-terminal telopeptide (NTx) levels in both crevicular fluids were determined by ELISA. PD was significantly reduced from years 2 to 3 appointments at implant sites as at teeth sites. At the 3-year appointment in both compartments, fluid volumes were significantly increased, which corresponded well with ascending NTx levels. The total amount of calprotectin decreased non-significantly in both GCF and PCF samples. Periapical radiographs revealed stable bone conditions around implants without significant changes from years 2 to 3 examinations. Clinical peri-implant parameters were considered as stable as the periodontal parameters of their corresponding teeth. A parallel increase in NTx levels in both GCF and PCF at 3-year appointment is not clearly understood; it may reflect an upregulation in the overall bone turnover rate.