Hard and soft tissue augmentation of vertical ridge defects with the “hard top double membrane technique”: introduction of a new technique and a case report

<abstract> <p>Vertical ridge defects (VRD) of the jaws often require both bone and keratinized mucosa (KM) reconstruction. A new staged procedure is proposed to restore both hard and soft tissues in the VRD through a case report. A patient required the lower right second premolar and first molar rehabilitation. The first surgery aimed to restore the bone architecture through the use of a titanium reinforced dense-PTFE (TR-dPTFE) membrane, positioned and stabilized on top of tenting screws. This membrane didn't cover the whole defect, it just created an hard top that avoided the collapse of a collagen membrane that was placed over it. This resorbable membrane was stabilized with tacks and covered the whole defect, protecting a mixture of autogenous bone and porcine xenograft both lingually and buccally. The second surgery was performed after a 5 month healing time either to remove the tenting screws and the TR-dPTFE membrane, and to augment KM with a gingival graft harvested from the palate. Both regenerated hard and soft tissues were left to mature for 7 months before the third surgery. In this last stage implants insertion and healing abutments application were carried out in a straightforward way, since bone and KM had been previously restored. Two bone samples, harvested for histologic evaluation, stated a great amount of new bone formation. This new approach allowed inserting implants in matured and stable regenerated bone and augmented KM, avoiding the hard and soft tissue loss around implant neck that can affect the VRD treatments during healing.</p> </abstract>

Megakaryocyte-driven changes in bone health: lessons from mouse models of myelofibrosis and related disorders

Over the years, numerous studies demonstrated reciprocal communications between processes of bone marrow hematopoiesis and bone remodeling. Megakaryocytes, rare bone marrow cells responsible for platelet production, were demonstrated to be involved in bone homeostasis. Myelofibrosis, characterized by an increase in pleomorphic megakaryocytes in the bone marrow, commonly leads to the development of osteosclerosis. In vivo, an increase in megakaryocyte number was shown to result in osteosclerosis in GATA-1low, NF-E2-/-, TPOhigh, Mpllf/f;PF4cre, Lnk-/-, Mpig6b-/-, Mpig6bfl/fl;Gp1ba-Cr+/KI, Pt-vWD mouse models. In vitro, megakaryocytes stimulate osteoblast proliferation and have variable effects on osteoclast proliferation and activity through soluble factors and direct cell-cell communications. Intriguingly, new studies revealed that the ability of megakaryocytes to communicate with bone cells is affected by the age and sex of animals. This mini-review summarises changes seen in bone architecture and bone cell function in mouse models with an elevated number of megakaryocytes and the effects megakaryocytes have on osteoblasts and osteoclasts in vitro, and discusses potential molecular players that can mediate these effects.

The osteoporosis treatment by gene therapy: a current approach and challenges

Osteoporosis is a worldwide disease characterized by reduction of bone mass and alteration of bone architecture resulting in increased bone fragility and increased fracture risk. Although it is seen in all age groups, gender, and races, it is more common in Caucasians (white race), older people, and women. With an aging population and longer life span, osteoporosis is increasingly becoming a global epidemic. Currently, it has been estimated that more than 200 million people are suffering from osteoporosis. Moreover, osteoporosis results in a decreased quality of life, increased disability-adjusted life span, and big financial burden to health insurance systems of countries that are responsible for the care of such patients. Therefore, increasing awareness in medical field, which, in turn, facilitates increase awareness of the normal populace, will be effective in preventing this epidemic.

THE USE OF A CALCIUM-CONTAINING VITAMIN-MINERAL COMPLEX IN CHRONIC GENERALIZED PERIODONTITIS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

Витамин Д является жирорастворимым витамином, который в организме человека вырабатывается только при определённых условиях, когда ультрафиолетовые лучи солнечного света попадают на кожу человека. В организм человека витамин Д поступает в ограниченном количестве 20- 30% от потребности , в таких продуктах питания как: лосось(200-800 МЕ на 100 г), сметана-50 МЕ, печень говяжья-45МЕ, масло сливочное-10-150 МЕ, молоко, обогащённое витамином Д, желтки яиц-45 МЕ. Витамину Д для активации в организме необходимо пройти два процесса гидроксилирования. Первый из них происходит в печени (до 90%) и превращает витамин Д в 25-гидроксивитамин Д-25(ОН)Д или кальцидиол. Второй этап происходит в почках (10%), в результате чего синтезируется активный 1,25 -дигидроксивитамин Д или кальцитриол. Уровень образования Д-гормона в организме взрослого человека составляет около 0,3-1,0 мкг/сут. Важнейшая реакция, в которой участвует витамин Д - абсорбция кальция в кишечнике и его реабсорбция в почках, поддержание необходимого уровня кальция и фосфатов в крови, он необходим для роста костей и процессов костного ремоделирования. Чтобы сохранить нормальный гомеостаз кальция и костного ремоделирования, организму необходимо получать витамин D3. В условиях физиологии его потребность варьирует в сутки от двухсот-четырёхсот МЕ (у взрослых людей), до шестисот-восьмисот МЕ (у людей пожилого возраста) и до одной тысячи МЕ у лиц, живущих в районах Крайнего Севера. Концентрация промежуточного метаболита [25-(OH)D3] в сыворотке крови считается самым надёжным показателем общего обмена витамина D, поэтому этот показатель может быть использован для определения обеспеченности организма витамином D. Также он необходим для выяснения причин патологических концентраций кальция в сыворотке крови пациентов. Адекватное содержание [25-(OH)D3] поддерживает абсорбцию кальция и костный метаболизм. Содержание же [25-(OH)D3] ниже целевого значения 30 нг/мл вызывает снижение кальция в плазме крови и повышение секреции ПТГ, и как следствие, остеокластическую резорбцию кости, нарушение процессов ремоделирования и минерализации костной ткани, снижение её плотности и изменение костной архитектуры Vitamin D is a fat-soluble vitamin that is produced in the human body only under certain conditions, when ultraviolet rays of sunlight fall on the human skin. The human body receives vitamin D in a limited amount of 20-30% of the need, in such food products as: salmon (200-800 IU per 100 g), sour cream-50 IU, beef liver-45 IU, butter-10-150 IU, milk enriched with vitamin D, egg yolks-45 IU. Vitamin D needs to undergo two hydroxylation processes to be activated in the body. The first of these occurs in the liver (up to 90%) and converts vitamin D to 25-hydroxyvitamin D-25(OH)D or calcidiol. The second stage occurs in the kidneys (10%), resulting in the synthesis of active 1,25 -dihydroxyvitamin D or calcitriol. The level of D-hormone formation in the adult body is about 0.3-1.0 mcg/day. The most important reaction in which vitamin D is involved is the absorption of calcium in the intestine and its reabsorption in the kidneys, maintaining the necessary level of calcium and phosphates in the blood, it is necessary for bone growth and bone remodeling processes. To maintain normal calcium homeostasis and bone remodeling, the body needs to receive vitamin D3. In the conditions of physiology, its need varies per day from two hundred to four hundred IU (in adults), to six hundred to eight hundred IU (in the elderly) and up to one thousand IU in people living in the Far North. The concentration of the intermediate metabolite [25-(OH)D3] in the blood serum is considered the most reliable indicator of the total vitamin D metabolism, so this indicator can be used to determine the body's vitamin D supply. It is also necessary to find out the causes of abnormal concentrations of calcium in the blood serum of patients. Adequate [25-(OH)D3] content supports calcium absorption and bone metabolism. The content of [25-(OH)D3] below the target value of 30 ng / ml causes a decrease in calcium in the blood plasma and an increase in PTH secretion, and as a result, osteoclastic bone resorption, a violation of the processes of bone remodeling and mineralization, a decrease in its density and a change in bone architecture

Enthesis strength, toughness and stiffness: an image-based model comparing tendon insertions with varying bony attachment geometries

Tendons of the body differ dramatically in their function, mechanics and range of motion, but all connect to bone via an enthesis. Effective force transfer at the enthesis enables joint stability and mobility, with strength and stiffness arising from a fibrous architecture. However, how enthesis toughness arises across tendons with diverse loading orientations remains unclear. To study this, we performed simultaneous imaging of the bone and tendon in entheses that represent the range of tendon-to-bone insertions and extended a mathematical model to account for variations in insertion and bone geometry. We tested the hypothesis that toughness, across a range of tendon entheses, could be explained by differences observed in interactions between fibre architecture and bone architecture. In the model, toughness arose from fibre reorientation, recruitment and rupture, mediated by interactions between fibres at the enthesis and the bony ridge abutting it. When applied to tendons sometimes characterized as either energy-storing or positional, the model predicted that entheses of the former prioritize toughness over strength, while those of the latter prioritize consistent stiffness across loading directions. Results provide insight into techniques for surgical repair of tendon-to-bone attachments, and more broadly into mechanisms for the attachment of highly dissimilar materials.

Trabecular Bone Score and Bone Mineral Density in Postmenopausal Women with Morbid Obesity—A Clinical Paradox

Obesity has long been considered to have a protective effect on bone, but specific complications in those with morbid obesity are known to have a detrimental impact on bone architecture. We aimed to study the bone microarchitecture (TBS—trabecular bone score) and bone mineral density (BMD) in postmenopausal women with morbid obesity compared to obese and non-obese age-matched women. Eighty-five consecutive postmenopausal women with morbid obesity (body mass index (BMI) ≥ 35 kg/m2) were enrolled and compared to age-matched obese (n = 80) and non-obese postmenopausal controls (n = 85). The BMD and TBS were assessed in all subjects using a Hologic-QDR 4500-W Discovery-A DXA scanner. The mean BMD (gm/cm2) at the femoral neck in women with morbid obesity was found to be significantly lower as compared to the age-matched postmenopausal obese controls (0.723 versus 0.762, p-value = 0.002). The BMD at the lumbar spine and hip showed similar trends but were not statistically significant. The bone microarchitecture was found to be significantly lower in those with morbid obesity (1.205) as compared to the other two groups (obesity 1.244; non-obese 1.228) (p < 0.013). Though obesity was associated with a better bone density and bone microarchitecture in postmenopausal women, a paradoxical lower value was seen in those with morbid obesity.

Age-Dependent Changes in Bone Architecture, Patterning, and Biomechanics During Skeletal Regeneration

Mouse digit amputation provides a useful model of bone growth after injury, in that the injury promotes intramembranous bone formation in an adult animal. The digit tip is composed of skin, nerves, blood vessels, bones, and tendons, all of which regenerate after digit tip amputation, making it a powerful model for multi-tissue regeneration. Bone integrity relies upon a balanced remodeling between bone resorption and formation, which, when disrupted, results in changes to bone architecture and biomechanics, particularly during aging. In this study, we used recently developed techniques to evaluate bone patterning differences between young and aged regenerated bone. This analysis suggests that aged mice have altered trabecular spacing and patterning and increased mineral density of the regenerated bone. To further characterize the biomechanics of regenerated bone, we measured elasticity using a micro-computed tomography image-processing method combined with nanoindentation. This analysis suggests that the regenerated bone demonstrates decreased elasticity compared with the uninjured bone, but there is no significant difference in elasticity between aged and young regenerated bone. These data highlight distinct architectural and biomechanical differences in regenerated bone in both young and aged mice and provide a new analysis tool for the digit amputation model to aid in evaluating the outcomes for potential therapeutic treatments to promote regeneration.

FBW7 couples structural integrity with functional output of primary cilia

Structural defects in primary cilia have robust effects in diverse tissues and systems. However, how disorders of ciliary length lead to functional outcomes are unknown. We examined the functional role of a ciliary length control mechanism of FBW7-mediated destruction of NDE1, in mesenchymal stem cell (MSC) differentiation. We show that FBW7 functions as a master regulator of both negative (NDE1) and positive (TALPID3) regulators of ciliogenesis, with an overall positive net effect on primary cilia formation, MSC differentiation to osteoblasts, and bone architecture. Deletion of Fbxw7 suppresses ciliation, Hedgehog activity, and differentiation, which are partially rescued in Fbxw7/Nde1-null cells. We also show that NDE1, despite suppressing ciliogenesis, promotes MSC differentiation by increasing the activity of the Hedgehog pathway by direct binding and enhancing GLI2 activity in a cilia-independent manner. We propose that FBW7 controls a protein-protein interaction network coupling ciliary structure and function, which is essential for stem cell differentiation.

Complications of Paget bone disease: a study of 69 patients

Introduction: Paget bone disease (PBD) is characterized by a disorder in the bone remodeling activity at sites of involvement. This can produce dramatic alterations of local bone architecture and causes most of the complications. We aimed to focus on the characteristics of complications of PDB among hospitalized patients. Material and Methods: A retrospective study was conducted, on PBD patients hospitalized in two rheumatology centers from 1994 to 2019. Characteristics of the PBD complications were studied. Results: Sixty-nine patients were collected with a sex ratio of 0.76 and a mean age of 75.4±6.4 years [43-101]. The diagnosis of PBD was established in the average age of 64.2±11.5 years. The primary reason for consultation was pain (78.3%). The PBD was localized in the pelvis (58%), lower limb (42%), spine (36.2%), skull (23.2%) and upper limb (5.8%). It was polyostotic in 44.9% of cases. Dosage of ALP was 324 [68-8390]. The PDB complication rate was 52.2% and it decreased over time. The main complication was osteoarthritis (23.2%), followed by deafness (17.4%), fracture (15.9%), hydrocephalus (7.2%), neurological disease (7.2%) and osteosarcoma (1.4%). The presence of complications was significantly associated with the polyostotic form (p=0.01), the skull localization (p=0.04), an increased ALP (p=0.02). Conclusion: According to our study, the incidence rate of PBD among hospitalized cases is higher among elderly women and decreases over time. Complications related to PDB are frequent (52%). It concerns patients with a polyostotic form, skull localization and high ALP.