Pregnancy And Lactation-associated Osteoporosis Research Articles

Effective strategies for pregnancy and lactation-associated osteoporosis: teriparatide use in focus.

Pregnancy and lactation-associated osteoporosis (PLO) is a rare condition characterized by fragility fractures occurring during late pregnancy or lactation, primarily affecting the spine and causing significant morbidity and back pain. PLO can lead to mobility impairment and work incapacity, with recovery taking up to several years. Due to the lack of clinical trials, treatment strategies remain poorly defined, historically focusing on calcium supplements, vitamin D, and weaning from breastfeeding. However, recent attention has turned to teriparatide (TPD) as an option due to its anabolic properties and potential suitability for women of childbearing age. This review evaluates TPD's use in PLO treatment, using published systematic reviews and case studies. Over 300 cases with PLO were identified through PubMed, Google Scholar, and Cochrane searches until August 2023. We identified 175 cases with PLO treated with TPD alone or followed by antiresorptive therapy. Most women (85.7%) were primiparas. The mean ± SD duration of TPD use was 15 ± 6 months. Among the study patients, 91.4% used TPD alone, while 8.6% (15/175) utilized sequential therapy. Approximately 93% of our cohort exhibited potential risk factors for PLO. Despite the increased risk of recurrent fractures in PLO, only 14.7% (20/175) of those treated with TPD sustained new fractures during a 9-month to 9 years' follow-up period. The mean ± SD percent increase in BMD at the LS was 21.14% ± 7.4%, and at the FN it was 12.1% ± 9.3%. The baseline Z-scores at the LS ranged from -3.3 (-3.7 to -2.7), while the baseline Z-scores at the FN ranged from -2.0 (-2.7 to -1.5). This review emphasizes PLO severity, advocating for increased awareness and timely interventions. TPD emerges as a promising therapeutic option in certain cases.

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

The optimal management of pregnancy and lactation-associated osteoporosis (PLO) has not been designated. 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. 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. 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). 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.

Recent Insights into Pregnancy and Lactation-Associated Osteoporosis (PLO).

During pregnancy and lactation, female physiology adapts to fulfill the fetal and neonatal calcium and phosphorus requirements. The physiological changes that take place during these periods do not affect maternal skeleton resistance to fracture in most of the cases. However, there is a small percentage of women that do experience fragility fractures during these times of life. Pregnancy and lactation-associated osteoporosis (PLO) is an infrequent condition defined by the occurrence of non-traumatic fractures - most frequently vertebral - during the third trimester of gestation and/or the first months of postpartum. Its physiopathology has not yet been completely elucidated. Several authors have reported that risk factors for secondary osteoporosis might be present in up to 80% of the cases of PLO patients. According to recent studies, genetic factors might also play a relevant role in PLO. Given its rarity, the available literature on this condition is limited. Most of the published data consist on case reports and case series articles. There are not any randomized controlled trials regarding this disorder. Although there is consensus about discontinuation of lactation and calcium and vitamin D supplementation as the first steps in the treatment of these patients, there is still controversy regarding the long-term and/or pharmacological management of this condition. Recent data on the use of teriparatide in this population looks promising. In this review, we aimed to revise and summarize current knowledge about the physiopathology and management of PLO.

Clinical characteristics of pregnancy and lactation associated osteoporosis: An online survey study.

Pregnancy and lactationassociated osteoporosis (PLO) is a rare form of early-onset osteoporosis in which young women present with fractures, usually multiple vertebral fractures, during late pregnancy or lactation. Little information is available about etiology, clinical characteristics, risk factors and predictors of disease severity. PLO patients were recruited to complete an anonymized online questionnaire. Disease severity was defined as total number of fractures during or after the first pregnancy associated with a fracture(s). Analyses related disease severity to potential predictors including diseases/conditions or medication exposures. 177 completed surveys were received between 5/29/2018 and 1/12/2022. Average age at initial PLO fracture event was 32 ± 5years. The majority were primiparous with singleton pregnancy and 79% fractured during lactation. Subjects reported 4.7 ± 2.7 total PLO fractures, with 48% reporting ≥ 5 fractures. Vertebral fractures, reported by 164/177 responders (93%), were the most common fracture type. Conditions and medications most commonly reported included vitamin D deficiency, amenorrhea unrelated to pregnancy, nephrolithiasis, celiac disease (CD), oral steroid use, heparin products during pregnancy and progestin only contraceptive after pregnancy. CD and heparins exposure during pregnancy were significantly related to disease severity. This is the largest study characterizing clinical features of PLO to date. The large number of participants and broad range of clinical and fracture characteristics queried has yielded novel information on the characteristics of PLO and potential risk factors for its severity, including primiparity, exposure to heparin and CD. These findings provide important preliminary data that can help target future mechanistic investigations.

Bridging the Gap: Pregnancy-And Lactation-Associated Osteoporosis.

Early diagnosis of pregnancy- and lactation-associated osteoporosis (PLO) is mandatory for a good outcome. Standard care is not a matter of conventional guidelines, rather it requires an individualized strategy while true overall incidence and pathogeny remain open issues. This is a narrative review based on full-length English articles, published between January 2021 and March 2023 and accessed via PubMed (no traumatic fractures or secondary osteoporosis are included). Our case-sample-based analysis included 836 females with PLO (the largest cohort based on published cases so far) through 12 studies and 24 single case reports. Except for one survey, these involved retrospective cohorts of small size (6-10 females/study) to medium size (23-47 women/study), and large cohorts with >50 subjects per study (a maximum of 379). Age of diagnosis: from 24 to 40 years for case reports (most subjects being over 30 and primigravida), while original studies indicated an average age between 31 and 34.18 years. Type of fractures underlined a most frequent vertebral phenotype (a mean of 2 to 5.8 vertebral fractures per patient) versus a most severe non-vertebral phenotype (hip and femoral neck fractures mostly requiring surgery). Potential contributors varied: smoking (1/3-1/2 of subjects), family history of osteoporosis (1/3), heparin and glucocorticoid use in pregnancy, low body mass index (majority of cases), hypovitaminosis D; and (with a low level of statistical significance) anti-psychotic medication, gestational diabetes, lupus, thrombophilia, anemia, in vitro fertilization (1/3 in one study), twin pregnancy, tocolysis with MgSO4, and postpartum thyroiditis. Most remarkably, up to 50% of PLO patients harbor mutations of LRP5, WNT1, and COL1A1/A2 (more damaged form with potential benefits from osteoanabolic drugs); gene testing might become the new norm in PLO. The low index of clinical suspicion should be supported by performing magnetic resonance imaging (gold standard in pregnancy) with DXA (in lactation). Low bone mineral density is expected (Z-score varying from -2.2 SD to -4 SD, unless normal which does not exclude PLO). Bone turnover markers might be useful in individuals with normal DXA, in pregnancy when DXA cannot be performed, and in following the response to anti-osteoporosis drugs. Alternatively, microarchitecture damage might be reflected by DXA-trabecular bone score and high-resolution peripheral quantitative computed tomography. Specific medical interventions are currently focused on teriparatide (TPT) use (3 studies; n = 99 females treated with TPT and an additional subgroup of 18 patients from the gene-analysis-based study, thus a total of 117 females) which seems to be the therapy of choice as reflected by these new data: 6-24 months, 20 µg/day, no sequential therapy needed; case selection based on high fracture risk is necessary). The first case using romosozumab was reported in 2022. PAO/LAO remains a challenging condition which is a battle for the wellbeing of two individuals, on one hand, considering maternal-fetal outcomes and taking care of the offspring, but it is a battle for a multidisciplinary team, on the other hand, since a standardized approach is lacking.

Bone Microarchitecture and Strength Changes During Teriparatide and Zoledronic Acid Treatment in a Patient with Pregnancy and Lactation-Associated Osteoporosis with Multiple Vertebral Fractures

Pregnancy- and lactation-associated osteoporosis (PLO) is a rare form of osteoporosis, of which the pathogenesis and best treatment options are unclear. In this report, we describe the case of a 34-year old woman diagnosed with severe osteoporosis and multiple vertebral fractures after her first pregnancy, who was subsequently treated with teriparatide (TPTD) and zoledronic acid (ZA). We describe the clinical features, imaging examination, and genetic analysis. Substantial improvements were observed in areal and volumetric bone mineral density (BMD), microarchitecture, and strength between 7 and 40 months postpartum as assessed by dual-energy X-ray absorptiometry at the total hip and spine and by high-resolution peripheral quantitative CT at the distal radius and tibiae. At the hip, spine, and distal radius, these improvements were mainly enabled by treatment with TPTD and ZA, while at the distal tibiae, physiological recovery and postpartum physiotherapy due to leg pain after stumbling may have played a major role. Additionally, the findings show that, despite the improvements, BMD, microarchitecture, and strength remained severely impaired in comparison with healthy age- and gender-matched controls at 40 months postpartum. Genetic analysis showed no monogenic cause for osteoporosis, and it is suggested that PLO in this woman could have a polygenic origin with possible susceptibility based on familiar occurrence of osteoporosis.

Pregnancy and Lactation-Associated Osteoporosis Successfully Treated with Romosozumab: A Case Report

Pregnancy- and lactation-associated osteoporosis (PLO) is a rare type of premenopausal osteoporosis that occurs mainly in the third trimester or immediately after delivery; one of its most common symptoms is back pain caused by a vertebral fracture. The pathogenesis of PLO is unclear, and there is no accepted consensus regarding the treatment of PLO. Although treatments with drugs such as bisphosphonate, strontium ranelate, denosumab, and teriparatide were reported, there is no report of a patient with PLO treated with romosozumab. We present the first case of a patient with PLO treated with romosozumab following 4-month teriparatide treatment. A 34-year-old primiparous and breastfeeding Japanese woman experienced severe low back pain 1 month postdelivery. She was diagnosed with PLO on the basis of low bone marrow density (BMD) and multiple vertebral fractures with no identified cause of secondary osteoporosis. She was treated with teriparatide injection for 4 months, but the treatment was discontinued because of the patient feeling severe nausea after every teriparatide injection and the appearance of new vertebral fractures. Thereafter, we used romosozumab for 12 months. After the romosozumab treatment, her BMD was increased from the baseline by 23.6% at L1-L4, 6.2% at the femoral neck, and 11.2% at the total hip. Treating PLO with 12-month romosozumab after 4 months of teriparatide injection remarkably increased the BMD of the lumbar spine, femoral neck, and total hip without subsequent fracture. Romosozumab has potential as a therapeutic option to improve the BMD and reduce the subsequent fracture risk of patients with PLO.

Effect of Teriparatide on Subsequent Fracture and Bone Mineral Density in 47 Women with Pregnancy- and Lactation-associated Osteoporosis and Vertebral Fractures.

Introduction Pregnancy- and lactation-associated osteoporosis (PLO) with predominantly vertebral fractures is a rare but severe disease which can occur in the last trimester of pregnancy or postpartum. The aim of the present study was to assess the impact of teriparatide on subsequent fractures and bone mineral density (BMD) in patients with PLO. Materials and Methods A total of 47 patients with PLO and postpartum spinal fractures (mean: 4 fractures) undergoing treatment with teriparatide were investigated. The data collection period was set between 2006 and 2018. All patients received a subcutaneous injection of 20 µg teriparatide once a day for 24 months as well as individually adapted vitamin D supplementation. After 24 months of treatment, all women received no further treatment and either had regular menstrual cycles or took oral contraceptives. Fractures were confirmed by X-ray or MRI. Changes in BMD from baseline were examined using serial DXA measurements. Results After 24 months of teriparatide treatment, we could demonstrate an increase in BMD at the lumbar spine, femoral neck and total hip of + 30.1%, + 11.7% and + 12.2% respectively (p < 0.001 for all). At 12 months after cessation of treatment, BMD remained stable compared to the 24-month measurements at the lumbar spine, femoral neck and total hip which showed non-significant changes of + 1.4%, + 2.6% and + 4.1% respectively. Out of the 47 patients with PLO with a mean of 4 existing fractures, 4 patients (7.8%) sustained a subsequent fracture, two after 3 – 5 months of treatment and two at > 6 months of treatment. Conclusion 24 months of treatment with teriparatide in women with PLO and multiple vertebral fractures significantly increased BMD, predominantly BMD of the spine. As patients were premenopausal, there was no significant decrease in BMD in the following 12 months after cessation of treatment.

Pregnancy and Lactation Associated Osteoporosis (PLO)- Case Report

Pregnancy and Lactation Associated Osteoporosis (PLO)- Case Report

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 (20μg/day) (group A) plus calcium and vitamin D and eight women with calcium and vitamin D only (group B) for up to 24months. The primary end-point was between group differences in lumbar spine (LS) and total hip (TH) aBMD, and TBS at 12 and 24months. 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 12months, 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 24months, 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 24months.

Bone Density After Teriparatide Discontinuation With or Without Antiresorptive Therapy in Pregnancy- and Lactation-Associated Osteoporosis.

Pregnancy- and lactation-associated osteoporosis (PLO) is a rare and severe disorder that causes low-trauma or spontaneous fractures, most commonly multiple vertebral fractures, in the late pregnancy or lactation period[1]. In severe PLO, teriparatide (TPTD) might aid in bone mineral density (BMD) recovery and subsequent fracture risk reduction. However, it is unclear whether TPTD can be discontinued without sequential antiresorptive therapy (ART) in premenopausal women with PLO. In this retrospective cohort study, we investigated the changes in BMD in premenopausal women with PLO treated with TPTD 20 mcg daily with or without sequential ART. Data for 67 patients diagnosed with PLO from 2007 through 2017 were reviewed. Among 43 women with annual follow-up dual-energy X-ray absorptiometry data for 3years, 33 were treated with TPTD (median 12months) with (TPTD-ART, n = 13; median, 18months) or without (TPTD-no ART, n = 20) sequential ART. The two groups showed no differences in the mean age (31 vs. 31years), body mass index (BMI, 20.5 vs. 21.0kg/m2), and baseline lumbar spine (LS) BMD (0.666 vs. 0.707g/cm2; p > 0.05 for all). LSBMD increased at 1, 2, and 3years from baseline in both the TPTD-ART (14.1%, 21.8%, and 24.0%, respectively) and TPTD-no ART (17.3%, 24.1%, and 23.4%, respectively) groups, without significant between-group differences. Similar results were observed for the total hip BMD. LSBMD gain at 3years did not differ by ART use (adjusted β, 0.40; p = 0.874) in univariable and multivariable models adjusted for age, BMI, and baseline LSBMD. In summary, BMD gain by TPTD administration in premenopausal women with PLO can be well maintained without sequential ART treatment.

Influence of denosumab on bone mineral density in a severe case of pregnancy-associated osteoporosis

Pregnancy and lactation-associated osteoporosis (PLO) with predominantly subsequent vertebral fracture is a rare but severe disease with an estimated incidence of 0.4 in 100,000. In the past, patients with PLO have been predominantly treated with oral and i.v. bisphosphonates to reduce subsequent fracture risk. Hereby, the use of bisphosphonates in premenopausal women is controversial, as bisphosphonates know to persist in bone for many years and can be exposed and circulate in maternal serum and subsequently pass the placenta barrier and may have a detrimental effect on fetal bone health. Here we report the effects of denosumab on the bone mineral density (BMD) and subsequent fracture risk in PLO. In this case presentation, denosumab was administered postpartum with 3000 IE vitamin D and 1000 mg of calcium daily in a patient with PLO and vertebral fracture of L1 and L4. After 18 months of treatment with denosumab, we could demonstrate a clinical significant increase of BMD at the lumbar spine, femoral neck, and total hip of 32.2%, 13.0%, and 11.5% respectively with no further subsequent fractures. As the patient had regular menstrual cycles and considered a further pregnancy, denosumab treatment was terminated and soon a second pregnancy occurred. After the second pregnancy, BMD decreased at the lumbar spine, femur neck, and total hip by −8.8%, −6.9%, and −7.0% respectively compared to the maximum values during treatment with denosumab, but was still significantly higher compared to baseline levels with no further fractures.

Relevant genetic variants are common in women with pregnancy and lactation-associated osteoporosis (PLO) and predispose to more severe clinical manifestations.

Pregnancy and lactation-associated osteoporosis (PLO) is a rare skeletal disorder characterized by early-onset osteoporosis typically manifestating with vertebral compression fractures or transient osteoporosis of the hip. We hypothesized that genetic variants may play a role in the development of PLO. This study aimed to analyze the presence of genetic variants and a potential association with the clinical presentation in PLO. 42 women with PLO were included from 2013 to 2019 in a multicenter study in Germany. All cases underwent comprehensive genetic analysis based on a custom-designed gene panel including genes relevant for skeletal disorders. The skeletal status was assessed using dual-energy X-ray absorptiometry (DXA). Subgroups were further analyzed by serum bone turnover markers (n=31) and high-resolution peripheral computed tomography (HR-pQCT; n=23). We detected relevant genetic variants in 21 women (50%), with LRP5, WNT1 and COL1A1/A2 being the most commonly involved genes. The mean number of vertebral compression fractures was 3.3±3.4 per case with a significantly higher occurrence in the subgroup with genetic variants (4.8±3.7 vs. 1.8±2.3, p=0.02). Among the total cohort, DXA Z-scores were significantly lower at the lumbar spine compared to the femoral neck (p=0.002). HR-pQCT revealed a pronounced reduction of trabecular and cortical thickness, while trabecular number was within the reference range. Eighteen women (43%) received a bone-specific therapy (primarily teriparatide). Overall, a steep increase in bone mass (+37.7%) was observed after 3years. In conclusion, pregnancy and lactation represent skeletal risk factors, which may unmask hereditary bone disorders leading to PLO. These cases were affected more severely. Nevertheless, a timely diagnosis and adequate treatment can ensure a substantial recovery potential even without specific therapy. Patients with genetically induced low bone turnover (e.g.; LRP5, WNT1) may especially benefit from osteo-anabolic medication.

A Unique Case of Pregnancy and Lactation Associated Osteoporosis Presenting with a Clavicular Fracture: A Mini-Review of the Literature

Numerous cases of fragility fractures have been reported in young females in the clinical setting of pregnancy and/ or lactation, otherwise known as pregnancy and lactation associated osteoporosis (PLAO). The fractures reported in PLAO most commonly affect the vertebrae or hip. We present a case of PLAO and discuss its implications in a postpartum patient who suffered multiple atraumatic fractures involving her vertebrae, clavicle, rib, and pelvic rami while breastfeeding. This unique combination of fractures to our knowledge has not been reported in the. literature previously.

Challenges in the Management of Pregnancy and Lactation Associated Osteoporosis: Literature Review and Retrospective Study.

Pregnancy and lactation-associated osteoporosis (PLO) is a rare and special form of osteoporosis, which is poorly known with regard to its etiology, pathophysiology and therapy. However, PLO can cause vertebral compression fractures (VCFs) and height loss, which could cause further kyphosis of the spine. Therefore, PLO should be taken into account in the differential diagnosis when a woman presents with severe back pain during or after pregnancy. In our current study, we reviewed the novel literatures that demonstrate the current understanding of and treatment for PLO. In addition, we retrospectively studied four patients who suffered from back pain and VCFs during or after pregnancy. We also examine their clinical medicine treatment methods and outcomes in order to provide evidence for a better understanding of PLO and its relevant medical treatment.

A Postpartum Woman Diagnosed with Multiple Vertebral Fragility Fractures Due to Pregnancy and Lactation-Associated Osteoporosis

Pregnancy and lactation-associated osteoporosis (PLO) is a rare condition diagnosed with vertebral fractures detected in late pregnancy and early postpartum periods. The incidence of PLO is reported to be 0.4 in 100 000 women. Maternal bone resorption and absorption of calcium from the intestines are increased in order to ensure adequate calcium transfer to the fetus, 80% of which is in the last trimester. Bone mineral density decreases during lactation and is associated with high bone turnover. Although various factors have been suggested to be responsible, the cause and etiopathogenesis of osteoporosis associated with pregnancy and lactation have not been fully elucidated. Herein, we reported a 28 year-old primigravid woman without risk factors for secondary osteoporosis diagnosed with vertebral fractures at postpartum third month.

Challenges in the Management of Pregnancy and Lactation-Associated Osteoporosis (PLO) in Women of Childbearing age With Multiple Vertebral Fractures

Challenges in the Management of Pregnancy and Lactation-Associated Osteoporosis (PLO) in Women of Childbearing age With Multiple Vertebral Fractures

Annual report of the Women's Health Care Committee, Japan Society of Obstetrics and Gynecology, 2019.

Since 2010, the Women's Health Care Committee has continuously addressed issues closely linked to women's quality of life. The five agendas this committee has engaged for this academic year are as follows: (i) clinical study of urinary complications in perinatal and post-partum women's health care; (ii) enlightenment of infectious diseases in Obstetrics and Gynecology in Japan; (iii) educational activities regarding management guidelines for health care in female athletes; (iv) training program for women's health-care advisers; and (v) pregnancy- and lactation-associated osteoporosis (PLOP). The detailed activities of the five subcommittees are described herein. This report is based on the Japanese version of our annual report (Acta Obst Gynaec Jpn 2019;71(6): 889-898), which publicizes the activities of our committee.

Long-term outcome of patients with pregnancy and lactation-associated osteoporosis (PLO) with a particular focus on quality of life

Pregnancy and lactation-associated osteoporosis (PLO) is a very rare form of osteoporosis. Vertebral fractures either occur in the last trimester of pregnancy or after childbirth. Pathogenesis is still unclear. Until recently, almost no data existed in regards to the quality of life and long-term clinical outcome of patients with PLO. To determine the long-term clinical outcome of patients with pregnancy and lactation-associated osteoporosis (PLO) with respect to the following factors: pain, quality of life, mental condition, vertebral fractures, and capacity to work. In this single-center retrospective study, patients were reviewed for at least 2years, more than 50% of them were followed up until menopause. Bone density (DXA) and vertebral fractures were assessed. Standardized questionnaires were used to analyze factors such as quality of life (Qualeffo-41), anxiety and depression (PHQ-4), and pain (the visual analog scale [VAS]). Additionally, a questionnaire was designed in order to evaluate and discuss some of the reasons behind the occurrence of mental distress at the onset of symptoms. Our report shows the clinical course of 20 patients with PLO, 11 of them until menopause (on average 16.3years after onset of symptoms). When diagnosis was made, 5.4 vertebral fractures were noticed on average. Three of the 20 patients developed subsequent fractures in the following years. The diagnosis of PLO was made on average after 3.3months after the onset of symptoms. At the beginning of the investigation, physical and mental health of all patients were poor, but improved within the first 2years and continued doing so until menopause. The average time it took to return to employment was 3.3years. PLO has a significant impact on pain, mental state, quality of life, and capacity to work. However, the long-term prognosis is promising. The severe mental distress is presumably related to several contributing factors in life such as physical integrity and independence, family life, employment, and financial security.Key Points• PLO has a strong impact on quality of life and can lead to severe mental distress.• At onset of symptoms, patients with PLO are in very poor mental and physical condition; however, the long-term outcome after inpatient rehabilitation seems to be good.• Most patients do not suffer subsequent vertebral fractures until the menopause.

Women With Pregnancy and Lactation-Associated Osteoporosis (PLO) Have Low Bone Remodeling Rates at the Tissue Level.

Pregnancy and lactation-associated osteoporosis (PLO) is a rare, severe, early form of osteoporosis in which young women present with fractures, usually multiple vertebral fractures, during late pregnancy or lactation. In studies of idiopathic osteoporosis (IOP) in premenopausal women, we enrolled 78 women with low-trauma fractures and 40 healthy controls, all with normal menses and no secondary cause of bone loss. In 15 of the affected women, the PLO subgroup, fractures had occurred during late pregnancy or lactation. We hypothesized that clinical, bone structural, and metabolic characteristics would differ between women with PLO and those with (non-PLO) IOP and controls. All were evaluated > 12 months postpartum, when structural and remodeling characteristics would be expected to reflect baseline premenopausal status rather than transient postpartum changes. As previously reported, affected subjects (PLO and IOP) had BMD and microarchitectural deficiencies compared to controls. Women with PLO did not differ from those with IOP in terms of age, BMI, body fat, menarcheal age, parity, or age at first pregnancy. However, women with PLO had a more severe clinical presentation than those with IOP: more fractures (5.5 ± 3.3 versus 2.6 ± 2.1; p = 0.005); more vertebral fractures (80% versus 17%; p < 0.001); and higher prevalence of multiple fractures. BMD deficits were more profound and cortical width tended to be lower in PLO. PLO subjects also had significantly lower tissue-level mineral apposition rate and bone formation rates (0.005 ± 0.005 versus 0.011 ± 0.010 mm2 /mm/year; p = 0.006), as well as lower serum P1NP (33 ± 12 versus 44 ± 18 µg/L; p = 0.02) and CTX (257 ± 102 versus 355 ± 193 pg/mL; p = 0.01) than IOP. The finding that women with PLO have a low bone remodeling state assessed more than a year postpartum increases our understanding of the pathogenic mechanism of PLO. We conclude that women with PLO may have underlying osteoblast functional deficits which could affect their therapeutic response to osteoanabolic medications. © 2019 American Society for Bone and Mineral Research.