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Purpose of Review: Pseudohypoparathyroidism (PHP) is a disorder caused by mutations and/or epigenetic changes at the complex GNAS locus. It is characterized by hypocalcemia, hyperphosphatemia, and an elevated parathyroid hormone concentration secondary to the resistance of target tissues to the biological actions of parathyroid hormone. PHP is divided into several subtypes with different yet overlapping phenotypes. Research on the bone status in patients with PHP is sparse and has yielded inconsistent results. This review was performed to summarize the current knowledge on the bone phenotypes and possible mechanisms of PHP., Recent Findings: Patients with PHP exhibit highly variable bone phenotypes and increased concentrations of bone turnover markers. Long-standing elevation of the parathyroid hormone concentration may lead to hyperparathyroid bone diseases, including rickets and osteitis fibrosa. Compared with normal controls, patients with PHP may exhibit similar, increased, or decreased bone mineral density. Higher bone mineral density has been found in patients with PHP type 1A than in normal controls, whereas decreased bone mass, osteosclerosis, and osteitis fibrosa cystica have been reported in patients with PHP type 1B, indicating more variable bone phenotypes in PHP type 1B. Bone tissues show partial sensitivity to parathyroid hormone in patients with PHP, leading to heterogeneous reactions to parathyroid hormone in different individuals and even in different regions of bone tissues in the same individual. Regions rich in cancellous bone are more sensitive and show more obvious improvement after therapy. Active vitamin D and calcium can significantly improve abnormal bone metabolism in patients with PHP., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: We sought to identify oral symptoms found in hyperparathyroidism and compare their rate of occurrence, as well as potential variations in sequelae between primary, secondary, and tertiary hyperparathyroidism. Materials and methods: Database searches were performed through EMBASE and PubMed, with a continual handsearch for relevant articles. PRISMA guidelines were followed. Results: Two hundred five articles including 245 patients were analyzed with data extraction. The average age was 34.02 years old (age range 1-83), with 91 male and 154 female patients (1:1.7 M/F ratio). Patients presented with symptoms including facial asymmetry or swelling (167/214 cases; 78.0%), oral pain (30/214; 14.0%), systemic symptoms (25/214; 11.7%), referrals or incidental findings (16/214; 7.5%), and neuropathy (6/214; 2.8%) independently and in combination together. Bony pathology occurred most often in the mandible (100/245 cases; 40.8%), while 72 cases were in the maxilla (29.4%) and 73 cases in both jaw bones (29.8%). Conclusions: Our data collection identifies a wide variation in the presentation of hyperparathyroidism. In order to be more certain of oral maladies from hyperparathyroidism, studies with large patient populations need to be conducted at healthcare centers to clarify the oral outcomes of hyperparathyroidism. Clinical relevance: What was thought to be a characteristic finding of HPT, mandibular radiolucency occurred in only a minor portion of cases. Furthermore, the pathognomonic sign of HPT on radiograph, loss of lamina dura, was only the third most common presentation. Bone pathology was most commonly reported in literature, but should not be assumed the only oral sequelae of hyperparathyroidism. [ABSTRACT FROM AUTHOR]

Osteitis fibrosa cystica ( OFC) is the most frequent type of osseous change in renal osteodystrophy affecting the majority of dialysis patients. Brown tumors are a severe form of OFC. The involvement of the craniofacial skeleton causing facial disfigurement in patients on dialysis appears to be limited to case reports. After searching PubMed, we performed a systematic review of 127 cases with a severe form of OFC resulting in a facial disfigurement to understand possible determinants for this condition. We found that since the first published case in 1974, and after a peak in 1996, there appears to be an increase in published reported cases. Only 27.6% of these cases were published in nephrology journals. The most common region for reported cases was North America. Mean age of these patients was 31.2 years with a mean dialysis duration of 7 years. Almost 67% were women, and almost all were on hemodialysis. The disease tended to most commonly localize to the maxilla (73.2%) and mandible (57.5%). As part of the treatment, 59% of patients had a parathyroidectomy. More than one-third (35.4%) had symptomatic improvement at follow-up. Mean follow-up was 1.6 years. Clinicians should be aware of this clinical presentation of a severe form of OFC and/or brown tumors. Timely diagnosis and intervention may help to prevent or decrease destructive bone changes and reduce negative psychological consequences of facial disfigurement. [ABSTRACT FROM AUTHOR]

Paget's disease is an intraepithelial adenocarcinoma, which appears on the nipple-areola complex or, in its extramammary form, on anatomical regions rich in apocrine glands. The exclusive location in the groin area, without compromising other sites, is rare and difficult to diagnose clinically. We present a case of a 72-year-old man with a localized lesion on his right groin of unknown evolution time, a history of Chagas' disease, high blood pressure, two cerebrovascular accidents and anticoagulation with warfarin, with a confirmed diagnosis of extramammary Paget's disease. We ruled out the presence of extracutaneous neoplasm and he was treated with imiquimod 5% cream during 24 weeks, showing improvement and without recurrences of the lesion after a 2-year follow-up period. The isolated localization of Paget's disease in the groin is extremely rare, having clinical manifestations that can be easily confused with other dermatoses, which delays diagnosis and treatment. Topical imiquimod is a safe and effective alternative when surgery is contraindicated or refused by the patient. [ABSTRACT FROM AUTHOR]

The article presents a study on chronic kidney disease (CKD) which is associated with changes in bone structure. Serum parathyroid hormone (PTH) level, an indicator of bone disease begins to increase in CKD. It also informs that there is an association between abnormal mineral metabolism and adverse cardiovascular outcomes in CKD. It further informs that 15.1 percent of the U.S. adult population has CKD which is associated with high morbidity and mortality.

Summary: A 49-year-old woman presenting with leg edema and progressive dyspnea on exertion was found to have a diastolic murmur. Echocardiography revealed increased left ventricular volume and severe aortic regurgitation (AR). She also had pain in her chest and left shoulder. Gallium scintigraphy showed increased uptake in the sternum, and further examination indicated chronic osteomyelitis in the sternum and the proximal portion of bilateral clavicles. Aortic valve replacement was performed and the ascending aorta was found to have inflammatory wall thickening with adhesion formation. Histological study and other postoperative examinations revealed Takayasu''s arteritis (TA). Involvement of bone is rarely described in TA, and typical manifestations such as claudication of extremities, decreased brachial artery pulse, and arteriogram abnormality were absent, which made the preoperative diagnosis difficult. Here we report a case of severe AR due to TA which presented much difficulty in the diagnosing process, because a rare complicated illness, osteomyelitis was clinically apparent and there were few clinical manifestations related to TA. [Copyright &y& Elsevier]

Abstract: The national Finnish guidelines for medical treatment of hip fracture patients are: osteoporosis medication and the daily concomitant use of vitamin D and calcium supplements. We investigated the post-fracture medical therapy for osteoporosis and the calcium and vitamin D therapy among hip fracture patients in two Finnish hospitals. The pre-fracture osteoporosis medication and use of calcium and vitamin D supplements of the patients were inquired on admission. The patient-specific use of osteoporosis medication and of prescribed calcium and vitamin D therapy during the follow-up time were checked from The Finnish Social Insurance Institution. At the end of the follow-up, those who were alive were inquired about the use of medication at the time. Eight percent of the 223 patients used osteoporosis medication and 8% used prescribed calcium and vitamin D supplements before the fracture. During the follow-up, the figures were 39% (52/133) and 53% (70/133), respectively, and at the end of the follow-up, correspondingly, 25% (29/114) and 44% (50/114). The follow-up time was 19.5–35 months. The post-fracture medical therapy for osteoporosis was insufficient. More effort should be focused on the secondary prevention following hip fracture in order to ensure the recommended treatment of osteoporosis. [Copyright &y& Elsevier]

Abstract: Despite being treated with antiresorptive drugs, the severe osteoporosis (SO) is being considered as a condition in which patients are still subject to one or more vertebral or femoral fractures, or non-vertebral or non-femoral fractures, i.e., of other parts of the body such as the wrist, shoulder, tibia, ribs or hip. These patients are defined as non-responders (NRs) to the antiresorptive therapy, and recent research has shown that they represent 10–25% of all SO patients. During the last almost 3 years a new drug has become available in Italy, called teriparatide (rh-PTH-1-34), produced in Escherichia coli using the recombinant-DNA technique. It shows remarkable trophic and anabolic actions on the bones, and proved to be very useful for treating the osteoporosis in general. This study describes our experience in using teriparatide for the treatment of SO in a sample of 141 elderly women of mean age 73.4±5.8 years, with a mean number of fractures of 3.0±0.85, with a spine deformity index (SDI) of 5.92±1.27 and a mean vertebral T-Score (L1–L4) of −3.15±0.39, and a mean femoral T-Score of −2.50±0.28. All these patients had been treated with antiresorptive drugs for at least 1 year: specifically 70 of them with Alendronate, 42 of them with Risedronate and 29 of them with Raloxifene. For 18 months, all these patients were injected subcutaneously with 20μg of teriparatide, with the daily addition of 1g of calcium and 880IU of vitamin D. The study was continued for 24 months, at the end of which the patients continued to take only calcium and vitamin D. The patients underwent a CBM-DEXA control of vertebral column and femur every 6 months, and they were also administered a Quality-of-Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO). The QUALEFFO (41 items) questionnaire to evaluate the changes in the quality-of-life (QoL) and the consumption of non-steroidal anti-inflammatory drugs (NSAIDs) was also recorded. The results showed that teriparatide protected 96.5% against new fractures (only five new fractures occurred), bone mineral density (BMD) increased approximately by 12% in the vertebral column and by 11% in the femur, consumption of NSAIDs was reduced at the early stage approximately 80%, the QoL improved considerably and remained so during the 18 months of teriparatide treatment, with only a slight decrease during the 6 subsequent months. [Copyright &y& Elsevier]

Osteomyelitis of the craniofacial skeleton closely resembles osteomyelitis elsewhere in the body in its pathophysiology and medical management; subsequent reconstruction after debridement remains distinctly challenging. The goals of reconstruction must include the restoration of the complex and readily visible morphology of the cranium and face, as well as the adequate return of vital sensory, expressive, and digestive functions. In this article, the various reconstructive modalities will be discussed including pedicled and nonpedicled flaps with or without an osseous component, nonvascularized bone grafts, alloplastic implants, and bone regeneration using protein therapy. Although reconstruction of craniofacial defects after osteomyelitis commonly proves formidable, the satisfactory return of form and function remains a plausible reconstructive goal. [ABSTRACT FROM AUTHOR]

The local delivery of antibiotics in the treatment of osteomyelitis has been used safely and effectively for decades. Multiple methods of drug delivery have been developed for the purposes of both infection treatment and prophylaxis. The mainstay of treatment in this application over the past 20 years has been non-biodegradable polymethylmethacrylate, which has the advantages of excellent elution characteristics and structural support properties. Biodegradable materials such as calcium sulfate and bone graft substitutes have been used more recently for this purpose. Other biodegradable implants, including synthetic polymers, are not yet approved for use but have demonstrated potential in laboratory investigations. Antibiotic-impregnated metal, a recent development, holds great promise in the treatment and prophylaxis of osteomyelitis in the years to come. [ABSTRACT FROM AUTHOR]

Appropriately designed antibiotic regimens are critical to the management of all stages of osteomyelitis, although goals of therapy may vary in different stages of infection. The most important consideration for antibiotic selection is spectrum of action. Route of administration by intravenous or oral route is less important than drug levels that are achievable at the site of infection. Outpatient parenteral therapy and use of oral agents has simplified delivery of long-term treatment regimens. There are few high-quality studies that compare specific treatment regimens or durations of therapy, and recommendations for drugs and duration of antibiotic therapy are based on expert opinion, case series, and extrapolations from animal models. Intravenous ?-lactams are the treatment of choice for methicillin-susceptible STAPHYLOCOCCUS AUREUS, but there are also oral options available. Vancomycin has been the treatment of choice for methicillin-resistant STAPHYLOCOCCUS AUREUS osteomyelitis, but there are several newer parenteral and oral agents for treatment of methicillin-resistant STAPHYLOCOCCUS AUREUS including linezolid and daptomycin. Rifampin combined with other staphylococcal agents may increase cure rates, especially for device-associated infections. Oral fluoroquinolones and parenteral ?-lactam agents can be used for treatment of gram-negative osteomyelitis, but increasing resistance has complicated management of these infections. [ABSTRACT FROM AUTHOR]

The diagnostic imaging of osteomyelitis can require the combination of diverse imaging techniques for an accurate diagnosis. Conventional radiography should always be the first imaging modality to start with, as it provides an overview of the anatomy and the pathologic conditions of the bone and soft tissues of the region of interest. Sonography is most useful in the diagnosis of fluid collections, periosteal involvement, and surrounding soft tissue abnormalities and may provide guidance for diagnostic or therapeutic aspiration, drainage, or tissue biopsy. Computed tomography scan can be a useful method to detect early osseous erosion and to document the presence of sequestrum, foreign body, or gas formation but generally is less sensitive than other modalities for the detection of bone infection. Magnetic resonance imaging is the most sensitive and most specific imaging modality for the detection of osteomyelitis and provides superb anatomic detail and more accurate information of the extent of the infectious process and soft tissues involved. Nuclear medicine imaging is particularly useful in identifying multifocal osseous involvement. [ABSTRACT FROM AUTHOR]

Skull-based osteomyelitis, which is a true bony infection, originates from a chronic, inadequately treated infection. Because of the complex craniofacial skeletal anatomy and associated aesthetic concerns, osteomyelitis of the craniofacial skeleton must be uniquely managed and is more difficult to treat than osteomyelitis of other bones of the body. It is thought that osteomyelitis is decreasing in prevalence due to broad-spectrum antibiotic treatment; however, it still remains a challenging clinical entity in developing countries and lower socioeconomic areas. [ABSTRACT FROM AUTHOR]

Long bone osteomyelitis presents a variety of challenges to the physician. The severity of the disease is staged depending upon the infection's particular features, including its etiology, pathogenesis, extent of bone involvement, duration, and host factors particular to the individual patient (infant, child, adult, or immunocompromised). Long bone osteomyelitis may be either hematogenous or caused by a contiguous spread of infection. A single pathogenic organism is almost always recovered from the bone in hematogenous osteomyelitis; STAPHYLOCOCCUS AUREUS is the most common organism isolated. A variety of multidrug-resistant organisms of bacteria continue to be a source of concern in arresting infection. The primary weapons to treat these infections are culture-specific antibiotics, aggressive debridement, muscle flaps, and bone grafts. This article offers a basic review of the classification, etiology, epidemiology, pathogenesis, and treatment of long bone osteomyelitis. [ABSTRACT FROM AUTHOR]

Abstract: Studies on the prevalence of site-specific osteoporosis in patients with different clinical presentations of primary hyperparathyroidism (PHPT) are scarce in the literature. The present study aims to determine the prevalence of cortical osteoporosis in such patients by using 3-site dual-energy X-ray absorptiometry (lumbar spine, femoral neck, 1/3 radius). We studied 49 patients, 12 males and 37 females, with PHPT, who were separated into 3 groups: asymptomatic (AS), renal stone disease (RS), and osteitis fibrosa cystica (OF). Osteoporosis occurred as follows: lumbar spine—48% for AS, 17.6% for RS, and 100% for OF (p =0.0004); femoral neck—20% for AS, 12% for RS, and 85.7% for OF (p =0.0014); 1/3 radius—71% for AS, 53% for RS, and 86% for OF (p =0.2845). Serum calcium, parathyroid hormone, alkaline phosphatase, and β-carboxy-terminal telopeptide were significantly higher in the OF group. The mean values for 25-hydroxyvitamin D were lower in OF group than AS and RS groups (15.2±6.3ng/mL vs. 22.7±11.9ng/mL and 20.3±7.0ng/mL; p =0.2139). Based on these results, we conclude that the prevalence of osteoporosis is high in all sites studied and is almost universal in the OF patients. The great prevalence of cortical osteoporosis is seen even in young patients with less severe forms of the disease. [Copyright &y& Elsevier]

Abstract: The World Health Organization fracture risk assessment tool (FRAX) uses clinical risk factors to predict the patient''s 10-yr probability of sustaining a hip or other major osteoporosis-related fracture. Inclusion of the femoral neck T-score is optional in the calculation. We evaluated the impact of including the T-score in the calculation of fracture risk and resultant treatment recommendation. We retrospectively reviewed charts of 180 white women scanned on a Hologic dual-energy X-ray absorptiometry (DXA). FRAX scores were calculated with T-scores (FRAX+) and without T-scores (FRAX−). We compared the National Osteoporosis Foundation (NOF) treatment recommendations (≥20% risk of a major osteoporotic fracture or ≥3% risk of hip fracture for osteopenic patients) between FRAX+ and FRAX− scores. Agreement between FRAX+ and FRAX− was 89.4%. Disagreement occurred in 2 distinct subgroups of patients (10.6% of cases), that is, FRAX+ scores exceeded the NOF recommended treatment thresholds and FRAX− scores did not, or vice versa. One subgroup comprised older patients with normal T-scores for whom FRAX− scores exceeded the treatment threshold. The second subgroup comprised younger patients with high body mass index (BMI) and low T-scores for whom FRAX− scores did not exceed the treatment threshold. FRAX scores generated without T-scores may lead to treatment recommendations for patients who have normal bone mineral density and no treatment recommendations for patients who have osteoporosis. T-scores should be used for optimal application of FRAX. [Copyright &y& Elsevier]

Osteoprotegerin (OPG) acts by neutralizing the receptor activator of nuclear factor-κB ligand (RANKL), the primary mediator of osteoclast differentiation, function, and survival. We examined whether OPG could affect the bone loss associated with chronic kidney disease (CKD) in a rodent model of CKD and secondary hyperparathyroidism (SHPT). SHPT was induced in rats by 5/6 nephrectomy (5/6 Nx) and a 1.2% P/0.6% Ca2+ diet. Starting 1 week after 5/6 Nx, rats were treated with vehicle (veh) or OPG-Fc (3 mg/kg, intravenously) every 2 weeks for 9 weeks. At baseline, 3, 6, and 9 weeks, blood was taken and bone mineral density (BMD) and bone mineral content (BMC) were assessed by dual-energy X-ray absorptiometry. Serum parathyroid hormone (sPTH) levels reached 912 pg/ml in 5/6 Nx rats vs. 97 pg/ml in shams at 9 weeks. OPG-Fc had no effect on sPTH or Ca2+ levels throughout the 9-week study, indicating that SHPT was a renal effect independent of bone changes. At 3 weeks, 5/6 Nx-veh rats had osteopenia compared with sham-veh rats and 5/6 Nx-OPG-Fc rats had significantly higher percent changes in whole-body BMC, leg BMD, and lumbar BMD versus 5/6 Nx-veh rats. By 6–9 weeks, elevated sPTH was associated with reversal of bone loss and osteitis fibrosa in the proximal tibial metaphysis. OPG-Fc decreased this sPTH-driven high bone turnover, resulting in augmented thickness of proximal tibial trabeculae in 5/6 Nx rats. Thus, RANKL inhibition with OPG-Fc can block the deleterious effects of continuously elevated sPTH on bone, suggesting that RANKL may be an important therapeutic target for protecting bone in patients with CKD and SHPT. [ABSTRACT FROM AUTHOR]

Background: We previously concluded from histomorphometric analysis that minimodeling contributes to bone formation in adynamic bone disease in patients with primary hypoparathyroidism. Presently we investigated whether this mechanism might be peculiar to adynamic bone disease. Methods: We histomorphometrically analyzed bone specimens obtained at biopsy or autopsy from 26 maintenance hemodialysis patients with hyperparathyroidism necessitating parathyroidectomy (group A) and from 27 dialysis patients with hypoparathyroidism (group B); respective mean ages were 60 +/- 7 years vs. 64 +/- 8 years; dialysis duration 14 +/- 6 years vs. 11 +/- 9 years; and serum intact parathyroid hormone (PTH) 1205 +/- 439 pg/mL vs. 41 +/- 27 pg/mL. Group B was divided further into outpatient and inpatient subgroups. Results: By histomorphometry, group A patients were diagnosed with osteitis fibrosa, and those in group B with adynamic bone disease. Minimodeling bone volume and minimodeling bone number were significantly greater in group B than group A (P= 0.0028 and P= 0.0008, respectively). Minimodeling bone volume correlated significantly and positively correlated with total bone volume in group B (P= 0.0016), but not in group A. In group B, minimodeling bone volume and total bone voluem were greater in outpatients than inpatients (P < 0.0001 and P= 0. 025, respectively). Minimodeling bone volume and total bone volume showed significant negative correlation with age in group B (P < 0.001 and P= 0.005, respectively). Conclusion: Minimodeling might contribute to bone formation in dialysis patients with adynamic bone disease, in the absence of remodeling stimulated by parathyroid hormone (PTH), especially in relatively young patients with good activities of daily living. [ABSTRACT FROM AUTHOR]

Provides an insight into the skeletal physiology of renal osteodystrophy complicating end-stage renal disease. Histological features of osteitis fibrosa cystica; Pathophysiology of the adynamic bone disorder; Diagnosis of renal osteodystrophy.