Pregnancy- and lactation-associated osteoporosis (PLO) is a rare type of premenopausal osteoporosis, typically occurring during the third trimester of pregnancy and the early postpartum lactation period. This report presents a case involving severe multiple vertebral fractures due to PLO with low bone mineral density (BMD) and heightened bone turnover. A 39-year-old primiparous Japanese woman reported low back pain (LBP) starting at 28 weeks of pregnancy. The pain temporarily improved after delivery, although the LBP recurred and worsened 2 months into breastfeeding. Thereafter, the patient visited the Obstetrics and Orthopedic departments. Plain radiographs of the thoracic and lumbar spine showed loss of vertebral body height at the T4-12 and L1-3,5 vertebrae, leading to a diagnosis of 13 fractured vertebrae. BMD and serum bone turnover markers revealed low bone density and heightened bone turnover. In the absence of any identified alternative cause of secondary osteoporosis, the diagnosis was severe PLO with 13 vertebral fractures related to pregnancy and lactation. After treatment with bisphosphonates and an active vitamin D analog, the patient exhibited an increased BMD and normalization of bone turnover and resumed regular daily activities. Although the optimal PLO treatment strategy remains uncertain, bisphosphonates are an option; however, bisphosphonates can potentially affect the fetus through placental transfer. Therefore, careful consideration is required for patients planning pregnancy. Despite bisphosphonates\' widespread use and cost-effectiveness, selecting PLO medications involves multiple factors, necessitating further research.

This study aimed to histologically evaluate the effects of XPEED® and SLA surface on the mineral apposition rate (MAR) at 3 and 5 weeks in titanium dental implants placed in human bone. In total, 17 titanium dental implants with XPEED® surface (n = 9) used as test and SLA surface (n = 8) used as control were included in this study. Each patient received four doses of tetracycline 500 mg at 12 h intervals 2 weeks prior to biopsy retrieval. Implant retrieval was performed, and retrieved biopsies were carefully treated for histomorphometric evaluation under epifluorescence microscopy. At 3 and 5 weeks, newly formed bone appeared in direct contact with both types of tested surfaces. At 3 weeks, the MAR value was, respectively, 2.0 (±0.18) μm/day for XPEED® implants and 1.5 (±0.10) μm/day for SLA implants (p = 0.017). At 5 weeks, lower MAR values for both XPEED® and SLA implants were noted, with 1.2 (±0.10) μm/day and 1.1 (±0.10) μm/day, respectively (p = 0.046). The overall evaluation by linear regression analysis for both time and implant surfaces showed a decreased osteoblast activity at 5 weeks compared to 3 weeks (p < 0.005). The results of the present study show that the bone apposition rate occurs faster around implants with XPEED® surface at 3 weeks and 5 weeks of healing. MAR values may support the use of implants with XPEED® surfaces in early loading protocols.

Introduction: Cannabidiol (CBD), a nonintoxicating cannabinoid, may be involved in bone remodeling, but human studies are limited. In this case series, we explored the effects of oral CBD administration on bone turnover. Materials and Methods: Two postmenopausal women with osteopenia (T-score=-1 to -2.5) were randomized to receive 100 or 300 mg CBD daily (oral, bis in die [twice per day]) for 12 weeks. Serum markers of bone resorption (carboxyl-terminal collagen crosslinks [CTx]) and bone formation (procollagen type 1 N-terminal propeptide [P1NP], bone-specific alkaline phosphatase [BSAP], and osteocalcin [OC]); safety measures; plasma concentrations of CBD and metabolites; sleep disturbance; symptoms of depression, anxiety, and stress; and quality of life, were assessed. Results: CBD was well tolerated, with no clinically significant change in vital signs, hematology, chemistry, or urinalysis, and no adverse events reported. Reductions (% change vs. baseline) in CTx (-8.5%, -28.1%), P1NP (-9.9%, -39.5%), BSAP (-12.7%, -74.8%), and OC (-16.0%, -6.7%) were observed after 12 weeks of oral administration of 100 or 300 mg CBD daily, respectively. The two participants self-reported consuming 95.3% and 98.8% of CBD doses, respectively. CBD and select metabolites were measurable in plasma after 4 and 12 weeks of CBD treatment. No notable changes in sleep disturbance, depression, anxiety, stress, or quality of life were observed. Conclusions: CBD was well tolerated after 12 weeks of twice-daily oral administration and was associated with reduction in measured markers of bone turnover. Compliance with CBD treatment was good. Large-scale randomized clinical trials into the bone protective effects of CBD in postmenopausal women are warranted.

UNASSIGNED: Progressive osseous heteroplasia (POH) is an ultrarare genetic disorder characterized by an inactivating mutation in the GNAS gene that causes heterotopic ossification. Inhibition of the mammalian target of the rapamycin (mTOR) signalling pathway has been proposed as a therapy for progressive bone fibrodysplasia and non-genetic forms of bone heteroplasia. Herein, we describe the impact of using Everolimus as a rescue therapy for an identical twin girl exhibiting an aggressive clinical phenotype of POH.
UNASSIGNED: Clinical evaluation of the progression of the disease during Everolimus treatment was performed periodically. Cytokine markers involved in bone metabolism and protein markers related to bone activity were analyzed to explore bone turnover activity.
UNASSIGNED: The patient received Everolimus therapy for 36 weeks. During treatment, no clinical improvement of the disease was perceived. Analysis of biochemical parameters, namely, β-CTX (r 2 = -0.576, P-value = 0.016) and PNIP (r 2 = -0.598, P-value = 0.011), indicated that bone turnover activity was significantly reduced. Additionally, bone metabolism-related biomarkers showed only a significant positive correlation with PTH levels.
UNASSIGNED: Everolimus treatment did not modify the clinical progression of the disease in an aggressive form of POH, although an impact on the protein markers studied was observed.

External root resorption is an irreversible loss of dental hard tissue as a result of odontoclastic action. Multiple external cervical root resorptions in permanent teeth are rare. The exact cause of external cervical root resorption is unclear. It is currently well established that RANK/RANKL signaling is essential for osteoclastogenesis and osteoclast-mediated bone resorption. Denosumab is an anti-RANKL antibody used for the treatment of postmenopausal osteoporosis. RANK/RANKL pathway suppression by denosumab is expected to suppress the activity of clastic cells responsible for hard tissue resorption involving both osteoclasts and odontoclasts.
This case report demonstrates aggressive and generalized idiopathic external cervical root resorption that started and advanced during ongoing antiresorptive therapy with the human monoclonal RANKL-blocking antibody denosumab without discontinuation of therapy in a 74-year-old female patient treated for postmenopausal osteoporosis. The extent of resorptive defects was too large and progressively led to fractures of the teeth. The number of teeth involved and the extend of destruction excluded conservative treatment. The affected teeth had to be extracted for functional prosthetic reconstruction.
This finding suggests that treatment with denosumab may be associated with severe and aggressive odontoclastic resorption of multiple dental roots despite an adequate inhibitory effect on osteoclasts in the treatment of osteoporosis. The RANKL-independent pathways of clastic cell formation are likely to be involved in this pathological process.

BACKGROUND: Increased bone turnover is frequently observed in advanced cancer and predominantly related to bone metastases or therapy. Cachexia represents an important cause of morbidity and mortality in cancer patients. Key features are weight loss, muscle wasting and chronic inflammation, which induce profound metabolic changes in several organs, including the bone. However, whether cachexia contributes to abnormal bone metabolism in cancer patients is unknown. Aim of the present study was to determine the potential correlation of bone turnover markers with body composition and laboratory parameters in treatment-naïve cancer patients.
METHODS: In this cross-sectional study we measured the levels of carboxy terminal telopeptide of collagen (CTX), an indicator of bone resorption, as well as osteocalcin (Ocn) and procollagen type I N-terminal propeptide (PINP), indicators of bone formation, in 52 cancer patients and correlated with body composition and laboratory parameters. Univariate and multivariate logistic analysis were performed to identify determinants of negative bone remodeling balance, estimated by CTX/Ocn and CTX/PINP ratio.
RESULTS: Based on weight loss, body mass index and muscle mass, patients were divided into a cachectic (59.6%) and a control (40.4%) group. After correcting for the presence of bone metastases, our results showed a significant upregulation of CTX in cachectic patients compared to non-cachectic cancer patients (median 0.38 vs 0.27 ng/mL, p < 0.05), with no difference in Ocn and PINP levels (mean 14 vs. 16 ng/ml, p = 0.2 and median 32 vs. 26 μg/L, p = 0.5, respectively). In addition, the CTX/Ocn and the CTX/PINP ratio were indicative of bone resorption in 68% and 60% of cachexia patients, respectively (vs. 20% and 31% in the control group, p = 0.002 and p = 0.06). The main determinants of the unbalanced bone turnover were hypoalbuminemia for the CTX/Ocn ratio (OR 19.8, p < 0.01) and high CRP for the CTX/PINP ratio (OR 5.3, p < 0.01) in the multivariate regression analysis.
CONCLUSIONS: CTX is substantially higher in cachectic patients compared to non-cachectic oncological patients and hypoalbuminemia as well as elevated CRP concentrations are independent predictors of a negative bone remodeling balance in cancer patients. These results strongly indicate that cachexia correlates with exacerbated bone turnover in cancer.

BACKGROUND: The objective of this case-control study was to investigate the association between denosumab use and the risk of developing external cervical resorption (ECR).
METHODS: Thirty-three patients ≥45 years old who were diagnosed with ECR were selected. Controls were matched to the cases based on sex and age (±5 years) in a 1:1 ratio. Confounders were classified into systemic factors, including a history of systemic sclerosis, hepatitis B, denosumab use, and bisphosphonate use, or local factors, including a history of traumatic occlusion, periodontal procedures (scaling and root planing and periodontal surgeries), and tooth extraction (excluding third molar extraction). Additionally, the number of remaining teeth in each subject was recorded using panoramic radiographs. The baseline characteristics of the 2 groups, including age, sex, and the number of remaining teeth, were compared using the chi-square and Mann-Whitney U tests. Binary logistic regression was used to determine the possible association between denosumab use and the risk of developing ECR (α < 0.05).
RESULTS: No significant differences in baseline characteristics were observed between the case and control groups (P > .05). After adjusting for systemic and local cofounders, denosumab use was significantly associated with the occurrence of ECR (odds ratio = 7.317; 95% confidence interval, 1.410-37.966; P < .05).
CONCLUSIONS: Based on the binary logistic regression model, denosumab use could significantly predict the risk of developing ECR.

Generalized occurrence of external root resorption in an adult patient is a rare finding. This case report describes external cervical root resorption extensively affecting the dentition that may be associated with the use and subsequent cessation of denosumab for the treatment of osteoporosis.

Current guidelines recommend that serum C-terminal telopeptide of type I collagen (CTX) and serum procollagen type 1 aminoterminal propeptide (PINP), measured by standardized assays, be used as reference markers in observational and interventional studies. However, there are limited data to determine whether serum CTX and PINP are associated with hip fracture risk among postmenopausal women. We determined the associations of serum CTX and serum PINP with hip fracture risk among postmenopausal women aged 50 to 79 years at baseline. We performed a prospective case-control study (400 cases, 400 controls) nested in the Women\'s Health Initiative Observational Study, which enrolled participants at 40 US clinical centers. Cases were women with incident hip fracture not taking osteoporosis medication; hip fractures were confirmed using medical records. Untreated controls were matched by age, race/ethnicity, and date of blood sampling. Serum CTX and serum PINP were analyzed on 12-hour fasting blood samples. The main outcome measure was incident hip fracture risk (mean follow-up 7.13 years). After adjustment for body mass index, smoking, frequency of falls, history of fracture, calcium and vitamin D intake, and other relevant covariates, neither serum CTX level nor serum PINP level was statistically significantly associated with hip fracture risk (CTX ptrend  = 0.22, PINP ptrend  = 0.53). Our results do not support the utility of serum CTX level or PINP level to predict hip fracture risk in women in this age group. These results will inform future guidelines regarding the potential utility of these markers in fracture prediction. © 2018 American Society for Bone and Mineral Research.

Duchenne muscular dystrophy (DMD) is an X-linked recessive muscle disease characterized by secondary osteoporosis and increased fractures. We describe the case of a 20-year-old boy with DMD suffering from back pain due to multiple vertebral fractures who was treated with teriparatide. Improvement of bone density, pain, and quality of life was achieved. DMD is an X-linked recessive muscle disease with secondary osteoporosis and related frequently occurring fractures. To date, only bisphosphonates have been used to treat osteoporosis in DMD. Black bear parathyroid hormone has been previously reported to enhance bone mass in the dystrophin-deficient mouse. This study reports the positive effect of osteoanabolic treatment with once-daily recombinant human parathyroid hormone 1-34 (rhPTH 1-34, teriparatide) in a 20-year-old DMD boy suffering from multiple vertebral fractures causing back pain. Bone formation and resorption markers (osteocalcin and C-telopeptide of type I collagen, respectively), as expected, increased within 6 months and intensity of back pain early decreased, with no pain reported after 6 months at visual analog scale. Over a 18-month period of treatment with teriparatide, bone mineral density and quality of life, assessed by the 36-item short-form questionnaire, considerably improved and no side effects were reported. Further studies on large cohorts are warranted to test the efficacy of this promising treatment for DMD related osteoporosis.