What Parents of Children Born with a Cleft Lip and/or Palate Want to Know About the Care for their Child.

OBJECTIVE: Adequate health information that matches the needs of care recipients is a prerequisite for patient-centered care. To facilitate the provision of tailored and timely information, it isimportant to understand the information needs of parents of children and adolescents with cleft lip and/or palate (CL/P) themselves, and in addition they were asked how they experienced the provided care-related information. DESIGN: A cross-sectional study employing questionnaires and semi-structured interviews. SETTING: Participants were recruited from a cleft palate-craniofacial care unit in a major tertiary hospital in the Netherlands. PARTICIPANTS: Participants were parents or guardians of children with CL/P, and two adolescents with CLP. They were recruited through the outpatient clinic during multidisciplinary consultation or after clinical admission. RESULTS: In total, fifty-five questionnaires were completed by parents or guardians and eleven interviews were conducted with nine parents of children with CL/P and two adolescents with CL/P. In general, participants reported to be satisfied with provided information during hospital admission or multidisciplinary cleft team consultations (mean 8.0, scale 0-10). In addition, 25.5% (n = 14) indicated that information to prepare for hospital admission was lacking (eg, practical information). Thematic qualitative analysis yielded five main information needs: 1) Clear communication during the care process, 2) Overview of the care trajectory, 3) Specific care plan information, 4) Presentation of information and 5) Guidance and support. CONCLUSIONS: Our findings emphasize the importance of gaining insights into wishes and information needs from care recipients who can provide insights in their information needs. With these findings, information provision should be redesigned to improve and to foster the further transition to family-centered care.

Long-Term Changes in Free Nipple Graft Morphology and Patient-Reported Outcomes in Gender-Affirming Mastectomies.

BACKGROUND: After gender-affirming mastectomies with free nipple grafts, satisfaction with nipples tends to fall short behind chest outcomes. This might be related to changes in nipple areolar complex (NAC) dimensions over time. Therefore, the aim of this study is to establish the long-term changes in NAC morphology and compare these to cisgender male NAC outcomes. MATERIALS: An observational, cross-sectional study was performed. Data from two prospective cohorts were collected: (1) transgender men after a mastectomy with free nipple grafts and (2) cisgender men (reference sample). Demographics and 3-D images were collected for both groups. NAC measurements were performed on the 3-D images at 4 time points (7-, 30-, 90- and 365-days postoperative) in transgender men and once in cisgender men. Furthermore, the BODY-Q (nipple module) was administered postoperatively at 30-, 90- and 365-days in transgender men. RESULTS: In total, 67 transgender and 150 cisgender men were included. NAC width and height in trans men changed from 21.5 mm (±2.7) to 23.8 mm (±3.9, p<0.001) and 16.2 mm (±2.5) to 14.7 mm (±3.0, p=0.01) within a year, respectively. On average, the NACs increasingly rotated 21 degrees in the latero-caudal direction (p<0.001). The mean NAC width and height in cisgender men were 28.1 mm (±5) and 20.7 mm (±4), being significantly larger than in transgender men. Satisfaction for size, shape and flatness decreased significantly after postoperative day 30 (p=<0.05) in transgender men. CONCLUSIONS: Morphology of and satisfaction with the NACs in transgender men significantly changed over time. Understanding and incorporating these differences into pre-operative counseling and surgical planning might help increase patient satisfaction. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Within-patient randomized clinical trial comparing incisional negative-pressure wound therapy with suction drains in gender-affirming mastectomies.

BACKGROUND: Incisional negative-pressure wound therapy (iNPWT) is widely adopted by different disciplines for multiple indications. Questions about the most appropriate uses and value of iNPWT have been raised. METHODS: An open-label within-patient RCT was conducted in transgender men undergoing gender-affirming mastectomies. The objective was to determine the effect of iNPWT as a substitute for standard dressing and suction drains on wound healing complications. One chest side was randomized to receive the iNPWT intervention, and the other to standard dressing with suction drain. The primary endpoints were wound healing complications (haematoma, seroma, infection, and dehiscence) after three months. Additional outcomes were pain according to a numerical rating scale and patient satisfaction one week after surgery. RESULTS: Eighty-five patients were included, of whom 81 received both the iNPWT and standard treatment. Drain removal criteria were met within 24 h in 95 per cent of the patients. No significant decrease in wound healing complications was registered on the iNPWT side, but the seroma rate was significantly increased. In contrast, patients experienced both significantly less pain and increased comfort on the iNPWT side. No medical device-related adverse events were registered. CONCLUSION: Substituting short-term suction drains with iNPWT in gender-affirming mastectomies increased the seroma rates and did not decrease the amount of wound healing complications. Registration number: NTR7412 (Netherlands Trial Register).

Functional Outcomes and Urological Complications after Genital Gender Affirming Surgery with Urethral Lengthening in Transgender Men.

PURPOSE: We determined the urological complications and lower urinary tract function after genital gender affirming surgery with urethral lengthening in transgender men. MATERIALS AND METHODS: A single center, retrospective cohort study was performed from January 2013 to January 2018. Patient demographics, medical history, perioperative data, surgical and urological complications, and preoperative and postoperative urological outcomes were obtained. RESULTS: Of the 63 patients included in the study 8 (13%) underwent metoidioplasty and 55 (87%) phalloplasty, comprised of 27 (43%) free radial forearm flap, 19 (30%) anterolateral thigh flap and 9 (14%) superficial circumflex iliac artery perforator flap surgeries. In phalloplasty the types of urethral lengthening were tube-in-tube free radial forearm flap in 27 (49%), free radial forearm flap (second fasciocutaneous flap) in 18 (33%), superficial circumflex iliac artery perforator flap in 5 (9%) or labial in 5 (9%). Mean followup was 23 months (range 12 to 71). Stricture formation occurred in 35 (63%) phalloplasty and 5 (63%) metoidioplasty cases. Urethral fistula formation occurred in 15 (27%) phalloplasty and 4 (50%) metoidioplasty cases. Mean time to strictures and fistulas was approximately 3 months. Overall 46 (73%) patients needed revision surgery because of fistulas/strictures. After treatment 44 (70%) patients were able to void from the tip of the phallus. No clinically relevant differences in International Prostate Symptom Scores, frequency volume charts and uroflowmetry were found preoperatively vs postoperatively. CONCLUSIONS: Genital gender affirming surgery with urethral lengthening is a complex procedure with a high complication rate. After treating complications no clinically relevant differences in urological functioning were recorded. The majority of transgender men could void from the tip of the penis and showed favorable urological outcomes.

Short-term cost-effectiveness of one-stage implant-based breast reconstruction with an acellular dermal matrix versus two-stage expander-implant reconstruction from a multicentre randomized clinical trial.

BACKGROUND: Implant-based breast reconstruction (IBBR) is the most commonly performed reconstructive procedure and its economic impact is significant. This study aimed to analyse whether a direct one-stage IBBR with use of an acellular dermal matrix (ADM) is more cost-effective than two-stage (expander-implant) breast reconstruction. METHODS: The BRIOS (Breast Reconstruction In One Stage) study was an open-label multicentre RCT in which women scheduled for skin-sparing mastectomy and immediate IBBR were randomized between one-stage IBBR with ADM or two-stage IBBR. Duration of surgery and hospital stay, and visits for the primary surgery, unplanned and cosmetic procedures were recorded. Costs were estimated at an institutional level. Health status was assessed by means of the EuroQol Five Dimensions 5L questionnaire. RESULTS: Fifty-nine patients (91 breasts) underwent one-stage IBBR with ADM and 62 patients (92 breasts) two-stage IBBR. The mean(s.d.) duration of surgery in the one-stage group was significantly longer than that for two-stage IBBR for unilateral (2·52(0·55) versus 2·02(0·35) h; P < 0·001) and bilateral (4·03(1·00) versus 3·25(0·58) h; P = 0·017) reconstructions. Costs were higher for one-stage compared with two-stage IBBR for both unilateral (€12 448 (95 per cent c.i. 10 722 to 14 387) versus €9871 (9373 to 10 445) respectively; P = 0·025) and bilateral (€16 939 (14 887 to 19 360) versus €13 383 (12 414 to 14 669); P = 0·002) reconstructions. This was partly related to the use of relatively expensive ADM. There was no difference in postoperative health status between the groups. CONCLUSION: One-stage IBBR with ADM was associated with higher costs, but similar health status, compared with conventional two-stage IBBR. Registration number: NTR5446 ( http://www.trialregister.nl).

Predictors of complications after direct-to-implant breast reconstruction with an acellular dermal matrix from a multicentre randomized clinical trial.

BACKGROUND: In the multicentre randomized trial BRIOS (Breast Reconstruction In One Stage), direct-to-implant (DTI) breast reconstruction with an acellular dermal matrix (ADM) was associated with a markedly higher postoperative complication rate compared with two-stage tissue expander/implant breast reconstruction. This study aimed to identify factors that contribute to the occurrence of complications after DTI ADM-assisted breast reconstruction. METHODS: Data were obtained from the BRIOS study, including all patients treated with DTI ADM-assisted breast reconstruction. Logistic regression analyses were performed to identify factors predictive of postoperative complications. RESULTS: Fifty-nine patients (91 breasts) were included, of whom 27 (35 breasts) developed a surgical complication. Reoperations were performed in 29 breasts (32 per cent), with prosthesis removal in 22 (24 per cent). In multivariable analyses, mastectomy weight was associated with complications (odds ratio (OR) 1·94, 95 per cent c.i. 1·33 to 2·83), reoperations (OR 1·70, 1·12 to 2·59) and removal of the implant (OR 1·55, 1·11 to 2·17). Younger patients (OR 1·07, 1·01 to 1·13) and those who received adjuvant chemotherapy (OR 4·83, 1·15 to 20·24) more frequently required reoperation. In univariable analyses, adjuvant radiotherapy showed a trend towards more complications (OR 7·23, 0·75 to 69·95) and removal of the implant (OR 5·12, 0·76 to 34·44), without reaching statistical significance. CONCLUSION: Breast size appeared to be the most significant predictor of complications in DTI ADM-assisted breast reconstruction. The technique should preferably be performed in patients with small to moderate sized breasts. Registration number: NTR5446 ( http://www.trialregister.nl).

The assessment of sexual wellbeing in treatment-seeking transgender individuals: a systematic review of the medical literature.

Sexual-wellbeing is recognized as an important aspect of quality-of-life. Yet, no overview exists of which aspects of sexual-wellbeing have been assessed in trans individuals seeking or undergoing medical treatment, nor is it clear what tools are used to evaluate the effect of medical treatment on sexual-wellbeing. First, to identify which topics pertaining to sexual-wellbeing have been assessed in transgender individuals in a medical context. Second, to determine which tools have been used for measuring aspects of sexual-wellbeing. A conceptual framework of sexual-wellbeing, was used as reference. A literature search (in PubMed, Embase, Cochrane Library) was performed up to March 10th, 2020. Studies that assessed aspects of sexual-wellbeing in transgender individuals' medical context were included in this review. Specific sexual topics addressed in each study were extracted by two independent reviewers. Thematic analysis was performed to identify sexual themes. Additionally, tools used to measure topics related to sexuality in transgender individuals were identified. In 172 papers, a total of 178 topics related to sexual-wellbeing were identified. Ten overarching themes were identified; sexuality, enacted sexual script, sexual activities, sexual relations, sexual response cycle, genital function, sexual function, sexual pleasure, sexual satisfaction, and quality-of-sex-life. Functional aspects of sexuality are assessed most frequently. A variety of methods was used to evaluate aspects related to sexual-wellbeing in trans individuals and over 50 different tools were identified. Self-developed questionnaires were used most frequently (n = 80), followed by chart reviews (n = 50), self-developed structured interviews (n = 37) and physical examination (n = 13). 23 previously developed questionnaires were used, all of which were developed for a cisgender population. Many studies in trans individuals touch on topics related to sexual-wellbeing, however, a comprehensive conceptualisation of (10 themes of) sexual-wellbeing is still lacking. Still, no valid tool exists for assessing sexual-wellbeing in the trans population, but is much needed.

A usability evaluation of the perceived user friendliness, accessibility, and inclusiveness of a personalized digital care pathway tool.

OBJECTIVE: This study aimed to acquire insight into the perceived user friendliness, accessibility and inclusiveness of a personalized digital care pathway. MATERIALS & METHODS: Usability of the tool was tested in an experimental setting. Mixed methods data collection consisted of scenario-based eye tracking tests in a web- or mobile-based prototype of the tool, followed by a questionnaire assessing user friendliness (System Usability Scale; SUS) and a structured interview. Inclusiveness was assessed by subgroup comparisons based on language proficiency, age and education level. Via purposive sampling a heterogeneous population of users (N = 24) was recruited. Eye tracking was used to measure gaze behavior. RESULTS: Overall, participants were satisfied with the tool (scale 0-10, 7.5; SD = 1.29). User friendliness of the mobile version (68.3; SD = 21.6) was higher than the web version (50.9; SD = 17.3) measured by SUS score (0-100). With regard to accessibility, eye tracking scenarios showed that the menu bar was hard to find (17% mobile, 55% web). In all scenario's, information was found faster in the mobile version than the web version. Attention was easily drawn to images. Regarding inclusiveness of the tool, we found significantly longer completing time of the scenario tasks for low language proficiency (p-value = 0.029) and higher age subgroups (p-value = 0.049). Lower language proficiency scored a significant lower SUS score (p-value = 0.012). CONCLUSIONS: Overall, user friendliness and accessibility were positively evaluated. Assessment of inclusiveness emphasized the need for tailoring digital tools to those with low language proficiency and/or an older age. Co-creation of digital care tools with users is therefore important to match users' needs, make tools easily understandable and accessible to all users, and ultimately result in better uptake and impact.

The development of burn scar contractures and impact on joint function, disability and quality of life in low- and middle-income countries: A prospective cohort study with one-year follow-up.

OBJECTIVE: The aim of this study was to assess the development of burn scar contractures and their impact on joint function, disability and quality of life in a low-income country. METHODS: Patients with severe burns were eligible. Passive range of motion (ROM) was assessed using lateral goniometry. To assess the development of contractures, the measured ROM was compared to the normal ROM. To determine joint function, the normal ROM was compared to the functional ROM. In addition, disability and quality of life (QoL) were assessed. Assessments were from admission up to 12 months after injury. RESULTS: Thirty-six patients were enrolled, with a total of 124 affected joints. The follow-up rate was 83%. Limited ROM compared to normal ROM values was observed in 26/104 joints (25%) at 12 months. Limited functional ROM was observed in 55/115 joints (48%) at discharge and decreased to 22/98 joints (22%) at 12 months. Patients who had a contracture at 12 months reported more disability and lower QoL, compared to patients without a contracture (median disability 0.28 versus 0.17 (p = 0.01); QoL median 0.60 versus 0.76 (p = 0.001)). Significant predictors of developing joint contractures were patient delay and the percentage of TBSA deep burns. CONCLUSION: The prevalence of burn scar contractures was high in a low-income country. The joints with burn scar contracture were frequently limited in function. Patients who developed a contracture reported significantly more disability and lower QoL. To limit the development of burn scar contractures, timely access to safe burn care should be improved in low-income countries.

Posterior lumbar interbody fusion using non resorbable poly-ether-ether-ketone versus resorbable poly-L-lactide-co-D,L-lactide fusion devices. Clinical outcome at a minimum of 2-year follow-up.

Previous papers on resorbable poly-L-lactide-co-D,L-lactide (PLDLLA) cages in spinal fusion have failed to report adequately on patient-centred clinical outcome measures. Also comparison of PLDLLA cage with a traditionally applicable counterpart has not been previously reported. This is the first randomized prospective study that assesses clinical outcome of PLDLLA cage compared with a poly-ether-ether-ketone (PEEK) implant. Twenty-six patients were randomly assigned to undergo instrumented posterior lumbar interbody fusion (PLIF) whereby either a PEEK cage or a PLDLLA cage was implanted. Clinical outcome based on visual analogue scale scores for leg pain and back pain, as well as Oswestry Disability Index (ODI) and SF-36 questionnaires were documented and analysed. When compared with preoperative values, all clinical parameters have significantly improved in the PEEK group at 2 years after surgery with the exception of SF-36 general health, SF-36 mental health and SF-36 role emotional scores. No clinical parameter showed significant improvement at 2 years after surgery compared with preoperative values in the PLDLLA patient group. Only six patients (50%) in the PLDLLA group showed improvement in the VAS scores for leg and back pain as well as the ODI, as opposed to 10 patients (71%) in the PEEK group. One-third of the patients in the PLDLLA group actually reported worsening of their pain scores and ODI. Three cases of mild to moderate osteolysis were seen in the PLDLLA group. Following up on our preliminary report, these 2-year results confirm the superiority of the PEEK implant to the resorbable PLDLLA implant in aiding spinal fusion and alleviating symptoms following PLIF in patients with degenerative spondylolisthesis associated with either canal stenosis or foramen stenosis or both and emanating from a single lumbar segment.

The ideal location of the male nipple-areolar complex: A pinpointing algorithm.

Background: In the treatment of gender dysphoria, appropriate nipple-areola complex (NAC) positioning is essential for achieving a natural appearing male chest after subcutaneous mastectomy. An accurate predictive model for the ideal personalized position of the NAC is still lacking. The aim of this study is to determine the anthropometry of the male chest to create individualized guidelines for appropriate NAC positioning in the preoperative setting. Materials and methods: Cisgender male participants were recruited. Multiple chest measurements were manually recorded. Best subset regression using linear models was used to select predictors for the horizontal coordinate (nipple-nipple distance; NN) and vertical coordinate (sternal notch-nipple distance; SNN) of the NAC. Internal validation was assessed using bootstrapping. Furthermore, a cohort of transgender men who had received a mastectomy with replantation of nipples according to current practice was identified. Comparison testing between the algorithm and standard practice was performed to test the limitations of standard practice. Results: One hundred and fifty cis male participants were included (median age: 26, IQR: 22-34 years). Four predictors were found to predict NN (age, weight, chest circumference (CC), anterior-axillar fold to anterior-axillar fold (AUX-AUX)) and reads as follows: NN = 4.11 + 0.035*age + 0.041*weight + 0.093*CC + 0.140*AUX-AUX Two predictors were found to predict SNN (NN and weight), and reads as follows: SNN = 7.248 + 0.303*NN + 0.072*weight. Both models performed well (Bootstrapped R2: 0.63 (NN), 0.50 (SNN)) and outperformed previous models predicting NAC position. Ninety-six transgender men were eligible for evaluation of current practice and showed an average placement error of -0.9 cm for NN and +2.2 cm for SNN. Conclusion: The non-standardized approach of NAC repositioning results in a significant error of nipple placement. We suggest that the two predictive models for NN and SNN can be used to optimize NAC positioning on the masculinized chest wall.Supplemental data for this article is available online at https://doi.org/10.1080/26895269.2021.1884926.

Resorbability of rigid beta-tricalcium phosphate wedges in open-wedge high tibial osteotomy: a retrospective radiological study.

The open-wedge high tibial osteotomy (OWHTO) is a well accepted treatment modality for patients with osteoarthritis of the medial compartment associated with genu varum. To fill in the osteotomy gap 30% macroporosity rigid beta-tricalcium phosphate (beta-TCP) is frequently used as a stable resorbable bone substitute. However, the resorbability of these beta-TCP wedges is not known. The aim of this study was to investigate this. Twenty-one OWHTO procedures in seventeen patients were performed with the use of 30% macroporosity rigid beta-TCP wedges. The osteotomies were fixed using an angle-stable locking plate. Conventional AP and lateral radiographs were examined in order to assess the resorbability of the 30% macroporosity rigid beta-TCP wedges as a function of time. A radiological classification system consisting of five phases was used to monitor the resorption of the 30% macroporosity rigid beta-TCP wedges. The mean duration of follow-up was 62 months (+/-23 range of 28-99). In all 21 cases, remnants of the 30% macroporosity rigid beta-TCP wedges were still present at maximum follow-up. Although the boundaries between 30% macroporosity rigid beta-TCP wedges and bone remained slightly visible, all osteotomies were completely consolidated and full osseointegration took place. In 16 out of 21 knees the fixation system was removed after a mean duration of 32 months (+/-19 range of 6-62). In six out of 21 knees a conversion to a knee arthroplasty was performed after a mean duration of 56 months (+/-18 range of 37-82). The OWHTO did not interfere with the placement of knee prostheses. Complete resorption of 30% macroporosity rigid beta-TCP wedges did not take place up to 8 years after operation.

Autologous fat grafting in onco-plastic breast reconstruction: A systematic review on oncological and radiological safety, complications, volume retention and patient/surgeon satisfaction.

OBJECTIVE: This study presents an up-to-date overview of the literature on autologous fat grafting (AFG) in onco-plastic breast reconstruction, with respect to complications, oncological and radiological safety, volume retention and patient/surgeon satisfaction. BACKGROUND: Although AFG is increasingly being applied in onco-plastic breast reconstruction, a comprehensive overview of the available evidence for this procedure is still lacking. METHODS: A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was conducted. Case series, cohort studies and randomized controlled trials (RCTs) reporting on relevant outcomes of breast reconstruction with supplemental AFG were included. RESULTS: In total, 43 studies were included reporting on 6260 patients with a follow-up period ranging from 12 to 136 months. The average locoregional and distant oncological recurrence rates after breast reconstruction with AFG were 2.5% (95% confidence interval (CI) 1.7-3.7) and 2.0% (95% CI 1.1-3.5), respectively. Fewer cysts and calcifications were seen on radiological images for this procedure than for other types of breast surgery. However, more biopsies were performed based on radiological findings (3.7% vs. 1.6%), and more cases of fat necrosis (9.0% vs 4.7%) were seen after treatment with AFG. The total complication rate of 8.4% (95% CI 7.6-9.1) is lower than those reported following other reconstructive breast procedures. The mean volume retention was 76.8% (range 44.7-82.6%) with a satisfaction rate of 93.4% for patients and 90.1% for surgeons. CONCLUSIONS: AFG in breast reconstruction is a promising technique. Safety is not compromised as cancer recurrence and complications are not observed. Whether AFG interferes with radiological follow-up remains to be elucidated. Randomized trials with sound methodology are needed to confirm these conclusions.

Single-stage breast reconstruction using Strattice™: A retrospective study.

INTRODUCTION: Strattice™, a porcine acellular dermal matrix, has emerged as a product to augment implant-based breast reconstruction. It aims to resolve problems related to poor tissue coverage of the implant. Presently, evidence justifying the use of Strattice in breast reconstruction is lacking. The objective of this study is to assess the clinical outcomes of a patient cohort that underwent single-stage implant-based breast reconstruction with the additional use of Strattice. METHODS: We conducted a retrospective chart review of patients who underwent single-stage breast reconstruction with the use of Strattice. All cases of breast reconstruction after oncologic or prophylactic mastectomy between 2010 and 2014 in one of eight different centres in the Netherlands were included. Patient demographics, treatment characteristics and clinical outcome data were collected. The outcomes were presented using descriptive statistics, and the associations were evaluated using Fisher's exact test. RESULTS: Eighty-eight patients who underwent either unilateral (60 patients) or bilateral (25 patients) (n = 110 breasts) single-stage breast reconstruction with the use of Strattice were identified. The indication for mastectomy was therapeutic in 69.1% (76) of cases and prophylactic in 30.9% (34) of cases. The reported minor complications included seroma (20.9%), skin necrosis (20.0%), wound dehiscence (11.8%), erythema/inflammation (14.5%) and infection (11.8%). In 22 breasts (22.7%), reoperation was necessary, with explantation of the implant in 11 breasts (11.8%). CONCLUSIONS: In this cohort, the total complication rate was very high (78%). Although most complications were minor, reoperation was performed in 22.7%, with explantation of the implant in 11.8% of breasts. We suggest that patient selection, experience of the surgeon and handling of early complications are factors playing a crucial role in the success of the operation. The use of a Strattice sheet in single-stage implant-based breast reconstruction may be a promising technique, but more evidence from prospective, randomized studies is necessary to justify its use. LEVEL OF EVIDENCE: IV.

Osteocytes and bone lining cells: which are the best candidates for mechano-sensors in cancellous bone?

Previously, we have investigated the possible role of osteocytes as mechano-sensors, and mediators of bone turnover. It was found that the proposed regulatory mechanism produced morphologies of trabecular bone, under particular loading conditions, which were consistent with morphogenesis and adaptation as seen in reality. The main objective of this study was to discern whether lining cells or osteoblasts could possibly play a similar role as effectively with regard to their capacity for self-optimization of the trabecular architecture, in terms of a low apparent mass to stiffness ratio. For that purpose the earlier analyses with osteocytes as mechano-sensors, distributed throughout the bone, were repeated for mechano-sensors located at bone surfaces only. Compared to the osteocyte model, the surface cell remodeling algorithm was reluctant to change its architecture, which implies that it is less sensitive to changes in the loading pattern. This resulted in less efficient bone adaptation, which was reflected by a considerably higher relative mass for a similar apparent stiffness in the loading direction. In other words, more mass is needed to obtain an equally stiff structure, at the apparent level, with respect to the externally applied loads. Furthermore, stresses and strains at the tissue level vary across a much wider range, relative to the osteocyte model, where the higher incidence of elevated strains indicates an increased failure risk. Therefore, we conclude that mechanical information at the bone surface may not be sufficient to adequately regulate functional bone adaptation.

Effect of mechanical set point of bone cells on mechanical control of trabecular bone architecture.

The architecture of trabecular bone is thought to be controlled by mechanosensitive bone cells, where hormones provide a background for their responses to mechanical signals. It has been suggested that, in osteoporosis, this response is hampered by changed hormonal levels, thereby increasing the mechanical set point of the cells, which would lead to bone loss. We have investigated if a temporary increase of the mechanical set point causes deterioration of trabecular bone architecture, such as seen in osteoporosis. Furthermore, the effects of a changed loading pattern were investigated for the same reason. For this purpose, we used a computer simulation model, which was based on the regulation of bone architecture by mechanosensitive osteocytes. It was found that a temporary shift of the mechanical set point causes no lasting changes in architecture. Although an increase of the mechanical set point induces bone loss, the mechanism of bone loss (trabecular thinning) differs from what is observed in osteoporosis (loss of whole trabeculae). Hence, a change of the mechanical set point alone cannot explain bone loss as seen in osteoporosis. On the other hand, the removal of load components in a particular direction resulted in irreversible loss of whole trabeculae. These results indicate that such temporary changes in loading patterns could be important risk factors for osteoporosis.

Osteocyte density changes in aging and osteoporosis.

Recently, it was suggested that osteocytes are involved in the regulation of bone remodeling. We have examined human trabecular bone of the iliac crest of fracture patients and control subjects to determine if osteoporosis is associated with changes in osteocyte density or osteocyte death. The relationships of these parameters with age was also investigated. It was found that osteocyte death was not related to age, nor was it increased in osteoporosis compared with the controls. In healthy adults ranging from 30 to 91 years, lacunar number per bone area decreases with advancing age, from about 210/mm(2) to 150/mm(2). Significantly higher lacunar and osteocyte numbers per bone tissue volume were found in osteoporotics than in controls (17,100 lacunae/mm(3) and 13,300 osteocytes/mm(3) vs. 12,900 lacunae/mm(3) and 10,500 osteocytes/mm(3), respectively), whereas lacunar area was significantly reduced in osteoporotics (from 44.1 mu m(3) to 39.1 mu m(2)). These findings are compatible with the hypothesis that, in osteoporosis, osteoblasts produce less bone per cell. This can in turn explain the reduced wall thickness, which has previously been described as characteristic for osteoporosis.

Proposal for the regulatory mechanism of Wolff's law.

It is currently believed that the trabecular structure in bone is the result of a dynamic remodeling process controlled by mechanical loads. We propose a regulatory mechanism based on the hypothesis that osteocytes located within the bone sense mechanical signals and that these cells mediate osteoclasts and osteoblasts in their vicinity to adapt bone mass. A computer-simulation model based on these assumptions was used to investigate if the adaptation of bone, in the sense of Wolff's law, and remodeling phenomena, as observed in reality, can be explained by such a local control process. The model produced structures resembling actual trabecular architectures. The architecture transformed after the external loads were changed, aligning the trabeculae with the actual principal stress orientation, in accordance with Wolff's trajectorial hypothesis. As in reality, the relative apparent density of the structure depended on the magnitude of the applied stresses. Osteocyte density influenced the remodeling rate, which also is consistent with experimental findings. Furthermore, the results indicated that the domain of influence of the osteocytes affects the refinement of the structure as represented by separation and thickness of the struts. We concluded that the trabecular adaptation to mechanical load, as described by Wolff, can be explained by a relatively simple regulatory model. The model is useful for investigating the effects of physiological parameters on the development, maintenance, and adaptation of bone.

Osteocyte density and histomorphometric parameters in cancellous bone of the proximal femur in five mammalian species.

The species-specific relationships between trabecular morphology and osteocyte density were investigated in the femoral heads of 30 adult animals of five mammalian species (rat, rabbit, Rhesus monkey, pig, and cow). Our hypothesis is that osteocytes are mechanosensory cells and are involved in the regulation of bone remodeling. According to the predictions from a simulation model, this hypothesis implies that the influencing distance of osteocytes, together with the magnitude of the mechanical loads, determines the thickness of trabeculae and that the number of osteocytes primarily affects the rate of bone remodeling. The number of osteocytes per bone volume ranged from 93,200 mm-3 in rat to 31,900 mm-3 in bovine cancellous bone. Osteocyte density was inversely related to the size of the species. Since basal metabolic output is related to body mass, we speculate that osteocyte density may be related to metabolic rates. Trabecular thickness was larger in the cow than in the other species, but the range of variation between species was relatively small. This agrees with the hypothesis that trabecular thickness is limited by the domain that can be regulated by an osteocyte and that this domain is of similar size regardless of the species. Only in the rat was trabecular thickness considerably smaller than in the other species. This is probably due to the presence of the cartilaginous growth plate in the femoral head of the rat. The relationships with species are different for osteocyte density than for morphometric parameters. Hence, our data support our hypothesis that osteocyte density is not directly associated with the macroscopic trabecular architecture.

A physiological approach to the simulation of bone remodeling as a self-organizational control process.

Although the capacity of bone to adapt to functional mechanical requirements has been known for more than a century, it is still unclear how the bone adaptation processes are regulated. We hypothesize that osteocytes are sensitive to mechanical loading and control the regulation of bone mass in their environment. Recently, simulation models of such a process were developed, using the finite element method. It was discovered that these models produce discontinuous structures, not unlike trabecular bone. However, it was also found that severe discontinuities violate the continuum assumption underlying the finite element method and that the solutions were element mesh dependent. We have developed a simulation model (which is physiologically and mechanically more consistent) which maintains the self-organizational characteristics but does not produce these discontinuities. This was accomplished by separating the sensor density and range of action from the mesh. The results clearly show that predicted trabecular morphology, i.e. sizes and branching of struts, depend on the actual relationship between local load, sensor density and range of influence. We believe that the model is suitable to study the relationship between trabecular morphology and load and can also explain adaptation of morphology, in the sense of 'Wolff's law'.