Hypophosphatasia (HPP) is a rare inherited disorder characterized by rickets and low circulating concentrations of total alkaline phosphatase (ALP) caused by mutations in ALPL. Severe HPP presents in childhood but milder forms can present in adulthood. The prevalence and clinical features of adult HPP are poorly defined. The aim of this study was to evaluate the prevalence and clinical significance of low serum total alkaline phosphatase (ALP) levels in a clinic‐based population of adult osteoporotic patients. We searched for patients with low ALP in a cohort of 3285 patients referred to an osteoporosis clinic over a 10‐year period and performed mutation screening of ALPL in those with low ALP (≤40 U/L) on two or more occasions. These individuals were matched with four clinic controls with a normal ALP. We also evaluated the prevalence of low ALP and ALPL mutations in 639 individuals from the general population from the same region. We identified 16/3285 (0.49%) clinic patients with low ALP and 14 (87.5%) had potentially pathogenic variants in ALPL. Eight of these individuals were heterozygous for mutations previously described in HPP and 2 were heterozygous for novel mutations (p.Arg301Trp and p.Tyr101X). These mutations were not found in clinic controls or in the general population. Eight patients with low ALP, including 4 with ALPL mutations, were treated with bisphosphonates for an average of 6.5 years. In these individuals, the rate of fractures during treatment was comparable to that in normal ALP clinic controls who were treated with bisphosphonates. We conclude that heterozygous loss‐of‐function mutations in ALPL are common in osteoporosis patients with low ALP. Further studies are required to determine how best these individuals should be treated. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Teriparatide (TPTD) is the most widely used anabolic agent in the treatment of patients with osteoporosis although its use is restricted in many countries. A recent randomised trial confirmed that TPTD was superior to risedronate at preventing vertebral fractures over a 2-year period. There is limited information on the relative effectiveness of TPTD compared with standard care in routine clinical practice. In this paper, we report the results of an extended observational study of 724 women referred to a specialist clinic with severe osteoporosis over an 11.5-year period, who were considered for TPTD therapy. Of these patients, 496 (68.5%) were treated with TPTD, whereas the remaining 228 (31.5%) received other treatments. This was either because they were unwilling or unable to self-inject (52.6%), because they had already been established on oral bisphosphonates (31.1%) or because of contraindications (12.7%). The TPTD group were younger than the standard care group (69.6 vs. 74.1 years) and had a lower 10-year fracture risk (25.7% vs. 28.6%). Those treated with TPTD had a greater increase in BMD at the lumbar spine compared with standard care (13.3% vs. 8.2%, p < 0.001) after approximately 2 years and had a lower incidence of vertebral fractures (4.8% vs. 10.1%, p = 0.01) over the course of our observation. There was no difference between groups with respect to either BMD change at the femoral neck or incidence of non-vertebral fractures. This study confirms that TPTD is superior to standard care at reducing the risk of vertebral fracture in patients with severe osteoporosis.

Objectives To ascertain OT and PT experiences of managing Hypermobility Spectrum Disorders (HSD) and hypermobile Ehlers-Danlos Syndrome (hEDS) patients, specifically the training and confidence levels of therapists, use of evidence-based practice, accessibility of pain management and clinical psychology services, and perceived usefulness of a specialist centre in Scotland. Methods A mixed-method survey was distributed to Rheumatology OTs/PTs in Scotland. It included multiple choice and open text questions, which were analysed to reflect therapist’s experiences and perception of service need. Results We found that therapists in Scotland do have expertise in the management of HSD/hEDS patients; however, this expertise tends to be concentrated in secondary care, which makes it difficult for patients who are managed in primary care to access. The majority of respondents reported lack of access to external training (80%). There was difficulty in referral to pain management services (55%), and clinical psychology (28%) amongst adult therapists. Paediatric services provided considerably better access to these disciplines. Of note, the majority of respondents were in favour of a specialist centre in Scotland for the training and education of therapists (94.7%) and the diagnosis and management of complex HSD/hEDS patients (73.7%). Conclusion More research is urgently needed to evaluate the effectiveness of therapy interventions to underpin a national guideline so that we can improve outcomes for HSD/hEDS patients. A specialist centre with expert and engaged clinicians would be a valuable asset in coordinating patient focused research and conducting good quality clinical trials.