Contributors to Secondary Osteoporosis and Metabolic Bone Diseases in Patients Presenting with a Clinical Fracture

Bours, S.; Geel, Tineke van; Geusens, Piet; Janssen, Marcel J.W.; Janzing, H; Hoffland, G.A.; Willems, Paul; Bergh, Joop van den

doi:10.1210/jc.2010-2135

Cited by 113 publications

(104 citation statements)

References 32 publications

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“…Serum testosterone, Pi, or IGFBP3 values did not correlate with any of the DXA-derived bone parameters and it thus remains unknown how these risk factors may influence bone health in ALL survivors during their later adulthood. Male hypogonadism is a significant risk factor for osteoporosis (28). It is important to ensure proper replacement therapy and follow the compliance in adult ALL survivors.…”

Section: Discussionmentioning

confidence: 99%

Long-term skeletal consequences of childhood acute lymphoblastic leukemia in adult males: a cohort study

Mäkitie

Heikkinen

Toiviainen-Salo

et al. 2013

European Journal of Endocrinology

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Objective: Long-term health sequelae of childhood-onset acute lymphoblastic leukemia (ALL) remain largely unknown. Low bone mineral content (BMC) and bone mineral density (BMD) are recognized complications, but it is unknown whether these persist until adulthood. We evaluated skeletal characteristics and their association with ALL therapy in long-term male ALL survivors. Design: This cross-sectional cohort study included 49 long-term male ALL survivors and 55 agematched healthy males. Methods: BMD and compression fractures were assessed by dual-energy X-ray absorptiometry; blood biochemistry was obtained for parameters of calcium homeostasis. Results: The ALL survivors (median age 29 years, range 25-38 years), assessed 10-38 years after ALL diagnosis, had lower lumbar spine (P!0.001), femoral neck (P!0.001), and whole-body (PZ0.017) BMD than expected based on normative values. When compared with the controls (median age 30 years, range 24-36 years), the ALL survivors had lower lumbar spine BMC (PZ0.014), lower whole-body BMC (P!0.001), and lower whole-body BMD (P!0.001), but the differences were partly explained by differences in height. Altogether, 20% of the ALL survivors had spinal compression fractures, but these were equally prevalent in the controls. Males diagnosed with ALL before age 5 years had significantly lower BMD values. Other recognized risk factors included untreated hypogonadism, vitamin D deficiency, hypophosphatemia, low IGF-binding protein-3, and low physical activity. Conclusions: At young adulthood, long-term male ALL survivors have significantly reduced BMC and BMD and a high prevalence of spinal compression fractures. Careful follow-up and active treatment of the recognized risk factors are warranted.

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Section: Discussionmentioning

confidence: 99%

Long-term skeletal consequences of childhood acute lymphoblastic leukemia in adult males: a cohort study

Mäkitie

Heikkinen

Toiviainen-Salo

et al. 2013

European Journal of Endocrinology

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“…Secondary osteoporosis is defined as bone loss that results from specific, well-defined, clinical disorders or medical treatments (1). The prevalence of secondary osteoporosis, in both men and women, is widely debated (1,2,3,4,5,6,7,8). In some studies 20-30% of postmenopausal women and more than 50% of men with osteoporosis are affected with the secondary form of the disease.…”

Section: Introductionmentioning

confidence: 99%

“…subclinical hypercortisolism (SH), celiac disease, etc.) (1,3,5,6,7,16). Moreover, the criteria used to define which patient should undergo additional evaluation (i.e.…”

Section: Introductionmentioning

confidence: 99%

Prevalence of subclinical contributors to low bone mineral density and/or fragility fracture

Eller-Vainicher

Cairoli

Zhukouskaya

et al. 2013

European Journal of Endocrinology

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Objective: The prevalence of subclinical contributors to low bone mineral density (BMD) and/or fragility fracture is debated. We evaluated the prevalence of subclinical contributors to low BMD and/or fragility fracture in the presence of normal 25-hydroxyvitamin D (25OHVitD) levels. Design: Prospective observational study. Methods: Among 1095 consecutive outpatients evaluated for low BMD and/or fragility fractures, 602 (563 females, age 65.4G10.0 years) with apparent primary osteoporosis were enrolled. A general chemistry profile, phosphate, 25OHVitD, cortisol after 1-mg overnight dexamethasone suppression test, antitissue transglutaminase and endomysial antibodies and testosterone (in males) were performed. Serum and urinary calcium and parathyroid hormone levels were also evaluated after 25OHVitD levels normalization. Vertebral deformities were assessed by radiograph. Results: In total, 70.8% of patients had low 25OHVitD levels. Additional subclinical contributors to low BMD and/or fragility fracture were diagnosed in 45% of patients, with idiopathic hypercalciuria (IH, 34.1%) and primary hyperparathyroidism (PHPT, 4.5%) being the most frequent contributors, apart from hypovitaminosis D. Furthermore, 33.2% of IH and 18.5% of PHPT patients were diagnosed only after 25OHVitD levels normalization. The subclinical contributors to low BMD and/or fragility fracture besides hypovitaminosis D were associated inversely with age (odds ratio (OR) 1.02, 95% CI 1-1.04, PZ0.04) and BMI (OR 1.1, 95% CI 1.05-1.17, PZ0.0001) and directly with fragility fractures (OR 1.89, 95% CI 1.31-2.73, PZ0.001), regardless of BMD. Conclusions: Subclinical contributors to low BMD and/or fragility fracture besides hypovitaminosis D are present in more than 40% of the subjects with apparent primary osteoporosis. Hypovitaminosis D masks a substantial proportion of IH and PHPT patients.

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“…Furthermore, P2X7 receptors were shown to mediate stimulation of periosteal and cancellous bone formation and the inhibition of cancellous bone resorption during growth [115]. The P2X7 receptor is highly polymorphic and a number of studies have shown that single nucleotide polymorphisms (SNPs) of the P2X7 receptor gene are associated with fracture risk, decreased bone mineral density and osteoporosis (see [222][223][224]365]). P2X7 receptors are also involved in the complex chain of events leading to the formation of human osteoclasts, and it was suggested that P2X7 receptor antagonists may be valuable for the management of osteoporosis and with disorders of remodelling, where there is reduced bone mass [366,367].…”

Section: Osteoporosismentioning

confidence: 99%

Purinergic signalling in the musculoskeletal system

Burnstock

Arnett

Orriss

2013

Purinergic Signalling

109

114

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It is now widely recognised that extracellular nucleotides, signalling via purinergic receptors, participate in numerous biological processes in most tissues. It has become evident that extracellular nucleotides have significant regulatory effects in the musculoskeletal system. In early development, ATP released from motor nerves along with acetylcholine acts as a cotransmitter in neuromuscular transmission; in mature animals, ATP functions as a neuromodulator. Purinergic receptors expressed by skeletal muscle and satellite cells play important pathophysiological roles in their development or repair. In many cell types, expression of purinergic receptors is often dependent on differentiation. For example, sequential expression of P2X5, P2Y 1 and P2X2 receptors occurs during muscle regeneration in the mdx model of muscular dystrophy. In bone and cartilage cells, the functional effects of purinergic signalling appear to be largely negative. ATP stimulates the formation and activation of osteoclasts, the bone-destroying cells. Another role appears to be as a potent local inhibitor of mineralisation. In osteoblasts, the bone-forming cells, ATP acts via P2 receptors to limit bone mineralisation by inhibiting alkaline phosphatase expression and activity. Extracellular ATP additionally exerts significant effects on mineralisation via its hydrolysis product, pyrophosphate. Evidence now suggests that purinergic signalling is potentially important in several bone and joint disorders including osteoporosis, rheumatoid arthritis and cancers. Strategies for future musculoskeletal therapies might involve modulation of purinergic receptor function or of the ecto-nucleotidases responsible for ATP breakdown or ATP transport inhibitors.

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Contributors to Secondary Osteoporosis and Metabolic Bone Diseases in Patients Presenting with a Clinical Fracture

Cited by 113 publications

References 32 publications

Long-term skeletal consequences of childhood acute lymphoblastic leukemia in adult males: a cohort study

Long-term skeletal consequences of childhood acute lymphoblastic leukemia in adult males: a cohort study

Prevalence of subclinical contributors to low bone mineral density and/or fragility fracture

Purinergic signalling in the musculoskeletal system

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