Teriparatide Treatment in Patients with Pregnancy- and Lactation-Associated Osteoporosis.

Pregnancy- and lactation-associated osteoporosis (PLO) is a rare disease, presenting in most cases with severe back pain due to low energy vertebral fractures (VFs). Our purpose was to assess the effect of teriparatide (TPTD) vs. conventional management on areal bone mineral density (aBMD) and trabecular bone score (TBS) in patients with PLO. A multicenter retrospective cohort study concerning premenopausal women with PLO. Nineteen women were treated with TPTD (20 µg/day) (group A) plus calcium and vitamin D and eight women with calcium and vitamin D only (group B) for up to 24 months. The primary end-point was between group differences in lumbar spine (LS) and total hip (TH) aBMD, and TBS at 12 and 24 months. Patients in group A had sustained a median of 4.0 VFs (3-9) vs. 2.5 VFs (1-10) in group B (p = 0.02). At 12 months, patients on TPTD vs. controls achieved a mean aBMD increase of 20.9  ±  11.9% vs. 6.2  ±  4.8% at the LS (p < 0.001), 10.0  ±  11.6% vs. 5.8  ±  2.8% at the TH (p = 0.43), and 6.7  ±  6.9% vs. 0.9  ±  3.7% in TBS (p = 0.09), respectively. At 24 months, seven patients on TPTD and six controls achieved a mean LS aBMD increase of 32.9  ±  13.4% vs. 12.2  ±  4.2% (p = 0.001). P1NP levels during the first month of TPTD treatment were positively correlated with the 1-year LS aBMD change (r = 0.68, p = 0.03). No new clinical fractures occurred while on-treatment. In patients with PLO, TPTD treatment resulted in significantly greater increases in LS aBMD compared with calcium and vitamin D supplementation at 12 and 24 months.

Efficacy of Antiosteoporotic Medications in Patients With Rebound-Associated Fractures After Denosumab Discontinuation.

Denosumab discontinuation results in rapid bone loss and increased risk of multiple rebound-associated vertebral fractures (RAVFs). The optimal treatment for patients who have sustained such fractures is currently unknown. We aimed to investigate the bone mineral density (BMD) changes achieved with various regimens in postmenopausal women who had sustained RAVFs after denosumab discontinuation in everyday clinical practice. In this multicenter, retrospective observational study, 39 Greek postmenopausal women from six regional bone centers throughout Greece with RAVFs after denosumab discontinuation were included. We collected BMD and fracture data before and 1 year after treatment with denosumab (n = 20), teriparatide (n = 8), zoledronate (n = 8) or teriparatide/denosumab combination (n = 3). Both lumbar spine (LS)-- and femoral neck (FN)-BMD were preserved with all regimens used. With the exception of zoledronate, a trend towards increase was observed with all regimens in LS-BMD. Three patients sustained additional fractures despite treatment reinstitution (2 with zoledronate and 1 with teriparatide). Among patients with RAVFs following denosumab discontinuation both antiresorptive (zoledronate and denosumab) and anabolic (teriparatide) treatment as well as the combination of denosumab with teriparatide seem to be effective in terms of BMD response.

Progression of Rebound-Associated Vertebral Fractures Following Denosumab Discontinuation Despite Reinstitution of Treatment: Suppressing Increased Bone Turnover May Not Be Enough.

Rebound-associated vertebral fractures (RAVFs) could occur in a minority of the patients who discontinue denosumab. In such patients, denosumab is often reinstituted to rapidly suppress bone turnover and avert the risk of additional fractures. Herein we report the cases of 2 patients who sustained RAVFs, and in whom resuming denosumab treatment did not avert the occurrence of new RAVFs a few months later, despite the suppression of bone turnover markers. It seems that denosumab reinstitution cannot completely eliminate the risk of new RAVFs and that the rebound of bone turnover may not be the sole mechanism to explain this phenomenon.

S1 Guidelines on Bone Impairment in Spinal Cord Injury.

During the acute and chronic phase of spinal cord injury (SCI) bone turnover and structure are affected. Bone mineral density of lower limbs is decreased up to 28%-50% below that of age-matched peers at 12-18 mo post injury. Coexisting secondary etiologies of osteoporosis may be present, and during ageing additional loss of bone occurs. All these compose a complex canvas of bone impairment after spinal cord injury and make the therapeutical approach challenging. The risk of fragility fractures is increased after the 2nd decade post SCI affecting the functionality and quality of life of individuals with SCI. Diagnostic flaws, lack of a ranking system to categorize the degree of bone impairment similar to the one of World Health Organization, and evidence-based clinical guidelines for management in SCI requires interdisciplinary cooperation and appropriate planning of future research and interventions. Spinal Cord Section of Hellenic Society of Physical Rehabilitation Medicine convened an expert panel working group on bone and spinal cord injury at the Pan-Hellenic Congress 2018 of PRM in Athens Greece, to establish an evidence-based position statement for bone loss in individuals with SCI of traumatic or non-traumatic etiology. This was reviewed by an International Task Force and used to create S1 Guidelines. This first version S1 guideline will work towards to provide help with prophylactic basic osteoporosis therapy diagnostic and therapeutic decisions in acute and chronic phase and rehabilitation countermeasures against osteoporosis related with spinal cord injury.

Bone And Soft Tissue Changes In Patients With Spinal Cord Injury And Multiple Sclerosis.

In patients with spinal cord injury and multiple sclerosis, deterioration of body composition (changes in bone, fat and muscle mass) is associated with increased risk for diseases such as coronary artery heart disease, non-insulin dependent diabetes mellitus, lipid metabolism abnormalities, and osteoporotic fractures in these patients. Immobility leads to a changing pattern of loading in the paralyzed areas, and secondary alteration in structure. However, bone and soft tissue changes in these patients are usually neglected. The purpose of this article is to update on the pathophysiological mechanisms leading to bone and soft tissue changes, and to increase the awareness of the treating physicians with respect to bone, muscle and fat loss and their consequences aiming to obtain measures to prevent bone and soft tissue loss in these patients.

Progression of multiple vertebral fractures after denosumab discontinuation under treatment with romosozumab. A case-report.

INTRODUCTION: Denosumab (Dmab) is widely used for the treatment of post-menopausal osteoporosis. Its discontinuation is sometimes accompanied by multiple vertebral fractures. Romosozumab (Rmab) has not been tested for its ability to prevent the rebound phenomenon. CASE PRESENTATION: We present the case of a 68-year-old female patient with post-menopausal osteoporosis under treatment with Rmab who presented with multiple vertebral fractures after denosumab discontinuation. The addition of Rmab did not prevent new-onset rebound-associated vertebral fractures. The patient discontinued Rmab and Dmab was re-initiated. After six months, no new vertebral fractures occurred, bone mineral density increased and bone turnover markers remained suppressed. DISCUSSION: Our clinical case illustrates the ineffectiveness of Rmab to prevent the multiple vertebral fracture cascade attributable to discontinuation of Dmab. We believe that treatment with Rmab might not be enough to prevent this phenomenon. Treatment with Dmab or possibly combination treatment with Dmab and Rmab could be another treatment option.

Comparative Effectiveness of Therapeutic Interventions in Pregnancy and Lactation-Associated Osteoporosis: A Systematic Review and Meta-analysis.

CONTEXT: The optimal management of pregnancy and lactation-associated osteoporosis (PLO) has not been designated. OBJECTIVE: To systematically review the best available evidence regarding the effect of different therapeutic interventions on bone mineral density (BMD) and risk of fractures in these patients. METHODS: A comprehensive search was conducted in PubMed/Scopus databases until December 20, 2022. Data were expressed as weighted mean difference (WMD) with 95% CI. The I2 index was employed for heterogeneity. Studies conducted in women with PLO who received any antiosteoporosis therapy were included. Studies including women with secondary causes of osteoporosis or with transient osteoporosis of the hip were excluded. Data extraction was independently completed by 2 researchers. RESULTS: Sixty-six studies were included in the qualitative analysis (n = 451 [follow-up time range 6-264 months; age range 19-42 years]). The increase in lumbar spine (LS) BMD with calcium/vitamin D (CaD), bisphosphonates, and teriparatide was 2.0% to 7.5%, 5.0% to 41.5%, and 8.0% to 24.4% at 12 months, and 11.0% to 12.2%, 10.2% to 171.9%, and 24.1% to 32.9% at 24 months, respectively. Femoral neck (FN) BMD increased by 6.1% with CaD, and by 0.7% to 18% and 8.4% to 18.6% with bisphosphonates and teriparatide (18-24 months), respectively. Meta-analysis was performed for 2 interventional studies only. Teriparatide induced a greater increase in LS and FN BMD than CaD (WMD 11.5%, 95% CI 4.9-18.0%, I2 50.9%, and 5.4%, 95% CI 1.2-9.6%, I2 8.1%, respectively). CONCLUSION: Due to high heterogeneity and lack of robust comparative data, no safe conclusions can be made regarding the optimal therapeutic intervention in women with PLO.

Robust Bioinformatics Approaches Result in the First Polygenic Risk Score for BMI in Greek Adults.

Quantifying the role of genetics via construction of polygenic risk scores (PRSs) is deemed a resourceful tool to enable and promote effective obesity prevention strategies. The present paper proposes a novel methodology for PRS extraction and presents the first PRS for body mass index (BMI) in a Greek population. A novel pipeline for PRS derivation was used to analyze genetic data from a unified database of three cohorts of Greek adults. The pipeline spans various steps of the process, from iterative dataset splitting to training and test partitions, calculation of summary statistics and PRS extraction, up to PRS aggregation and stabilization, achieving higher evaluation metrics. Using data from 2185 participants, implementation of the pipeline enabled consecutive repetitions in splitting training and testing samples and resulted in a 343-single nucleotide polymorphism PRS yielding an R2 = 0.3241 (beta = 1.011, p-value = 4 × 10-193) for BMI. PRS-included variants displayed a variety of associations with known traits (i.e., blood cell count, gut microbiome, lifestyle parameters). The proposed methodology led to creation of the first-ever PRS for BMI in Greek adults and aims at promoting a facilitating approach to reliable PRS development and integration in healthcare practice.

Sarcopenia in patients with diabetes mellitus.

INTRODUCTION: Diseases such as diabetes mellitus may be associated with adverse changes in body composition. Sarcopenia is characterized by a progressive and generalized loss of skeletal muscle mass and functionality. AIM: To investigate the relationship between type 2 diabetes mellitus (T2DM) and sarcopenia. MATERIALS AND METHODS: In a retrospective, non-randomized study, 35 T2DM patients, aged 20-80 years, were assessed for sarcopenia prevalence compared to controls (n=16). Appendicular skeletal mass (ASM) (kg) was measured, and sarcopenia was defined as SMI <7.0 and <5.7 kg/m2, in males and females, respectively, using the European Working Group on Sarcopenia in Elderly (EWGOSP) definition. Low physical performance was defined as a walking speed of <0.8 m/s. RESULTS: Incidence of sarcopenia was significantly higher in T2DM patients vs. controls (27% vs. 20%, p=0.01) and elderly vs. young participants (40% vs. 12%, p<0.001), respectively. Walking velocity was significantly lower in T2DM patients compared to male and female controls (1.08±0.22 vs. 1.23±0.18 and 1.07±0.26 vs. 1.26±0.16, respectively, p<0.001,). CONCLUSIONS: A moderate prevalence of sarcopenia in patients with type 2 diabetes mellitus was observed, which appeared to increase significantly in older men. Finally, incidence of T2DM displayed decreased physical performance in both genders.

Association of physical exercise and calcium intake with bone mass measured by quantitative ultrasound.

BACKGROUND: Interventions other than medications in the management of osteoporosis are often overlooked. The purpose of this study was to investigate the association of physical activity and calcium intake with bone parameters. METHODS: We measured the heel T-score and stiffness index (SI) in 1890 pre- and postmenopausal women by quantitative ultrasound (QUS) and assessed physical activity and dietary calcium intake by questionnaire. Participants were divided according to their weekly physical activity (sedentary, moderately active, systematically active) and daily calcium consumption (greater than or less than 800 mg/day). RESULTS: SI values were significantly different among premenopausal groups (p = 0.016) and between sedentary and systematically active postmenopausal women (p = 0.039). QUS T-scores in systematically active premenopausal women with daily calcium intake > 800 mg/day were significantly higher than those in all other activity groups (p < 0.05) independent of calcium consumption. CONCLUSIONS: Systematic physical activity and adequate dietary calcium intake are indicated for women as a means to maximize bone status benefits.

Prospective study of spinal orthoses in women.

BACKGROUND: There are not many clinical trials investigating the efficiency and compliance of using spinal orthoses in the management of osteoporosis. OBJECTIVES: The purpose of this study was to investigate the effect of long-term use and the compliance of spinal orthoses in postmenopausal women with vertebral fractures. STUDY DESIGN: Clinical trial of spinal orthoses in postmenopausal women. METHODS: Women were separated into groups wearing different types of orthoses (Spinomed, Osteomed, Spinomed active, and Spine-X). Isometric maximum strength of trunk muscles (F/Wabdominals-extensors) was calculated and back pain was assessed in all women. In addition, women completed a compliance questionnaire about the use of the orthoses. RESULTS: Spinomed decreased pain (p = 0.001) and increased trunk muscle strength (F/Wabdominals, p = 0.005 and F/Wextensors, p = 0.003, respectively). The compliance of wearing an orthosis for 6 months was 66%. CONCLUSION: The results suggest that orthoses could be an effective intervention for back pain and muscle strengthening in osteoporotic women. CLINICAL RELEVANCE: In women with established osteoporosis, wearing Spinomed orthosis for at least 2 h/day for 6 months decreased back pain significantly and increased personal isometric trunk muscle strength. All spinal orthoses could be valuable instruments to help all requested rehabilitation programs like spine muscles' strengthening and postural correct behavior, but only when used properly.

Impact on bone and muscle area after spinal cord injury.

Spinal cord injury (SCI) causes inactivation and consequent unloading of affected skeletal muscle and bone. This cross-sectional study investigated correlations of muscle and bone in spinal cord-injured subjects compared with able-bodied subjects. Thirty-one complete SCI paraplegics were divided according to the neurological level of injury (NLoI) into group A (n=16, above thoracic 7 NLoI, age: 33±16 years, duration of paralysis (DoP): 6±6 years) and group B (n=15, thoracic 8-12, age: 39±14 years, DoP: 5.6±6 years), compared with 33 controls (group C). All were examined with peripheral quantitative computed tomography at 66% of tibia length (bone and muscle area, bone/muscle area ratio). In able-bodied subjects, muscle area was correlated with bone area (P<0.001, r=0.88). Groups A and B differed significantly from the control group in terms of bone and muscle area (P<0.001). In paraplegics, less muscle per unit of bone area (bone/muscle area ratio) was found compared with controls (P<0.001). Bone area was negatively correlated with the DoP in the total paraplegic group (r=-0.66, P<0.001) and groups A and B (r=-0.77, P=0.001 vs r=-0.52, P=0.12, respectively). Muscle area and bone/muscle ratio area correlations in paraplegic groups with DoP were weak. Paraplegic subjects who performed standing and therapeutic walking had significantly higher bone area (P=0.02 and P=0.013, respectively). The relationship between bone and muscle was consistent in able-bodied subjects and it was predictably altered in those with SCI, a clinical disease affecting bone and muscle.

Assessment of musculoskeletal system in women with jumping mechanography.

The purpose of this study was to investigate and add reference data about the musculoskeletal system in women. The mechanography system of the Leonardo™ platform (Novotec, Germany) was used to measure parameters of movement (velocity, force, power) in 176 healthy Greek women aged 20-79 years, separated according to age decade in six groups: group 1 (n = 12), 20-29 years; group 2 (n = 14), 30-39 years; group 3 (n = 33), 40-49 years; group 4 (n = 59), 50-59 years including 21 postmenopausal; group 5 (n = 31), 60-69 years including 12 postmenopausal; and group 6 (n = 27), 70-79 years all postmenopausal. This system measures forces applied to the plate over time, calculates through acceleration the vertical velocity of center of gravity and using force and velocity it calculates power of vertical movements. All women performed a counter-movement jump (brief squat before the jump) with freely moving arms. Weight was recorded on the platform before the jump and height was measured with a wall-mounted ruler. Body weight and body mass index were gradually increased; on the contrary height and all movement parameters except force (velocity, power) were statistically decreased during aging and after menopause.